Temporomandibular Disorders

Number: 0028

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References


Policy

Scope of Policy

This Clinical Policy Bulletin addresses temporomandibular disorders.

  1. Medical Necessity

    For plans that cover treatment of temporomandibular disorder (TMD) and temporomandibular joint (TMJ) dysfunction, requests for TMJ surgery require review by Aetna's Oral and Maxillofacial Surgery patient management unit.  Reviews must include submission of a problem-specific history (i.e., Aetna Temporomandibular Disorder Questionnaire) and physical examination, TMJ radiographs/diagnostic imaging reports, patient records reflecting a complete history of 3 to 6 months of non-surgical management (describing the nature of the non-surgical treatment, the results, and the specific findings associated with that treatment), and the proposed treatment plan.  The provider will be notified of the coverage decision after review of all pertinent data.

    1. Diagnostic Testing

      Aetna considers the following medically necessary for diagnostic testing for TMJ/TMD using the following modalities:

      1. Examination including a history, physical examination, muscle testing, range of motion measurements and psychological evaluation as necessary; and
      2. Diagnostic X-rays - a single panoramic X-ray of the jaws is considered medically necessary for the initial evaluation of TMJ disorders. The current scientific literature does not show that additional x-rays will result in better, reproducible outcomes during the initial screening or when fabricating of a TMJD oral splint. Additional X-rays are considered medically necessary if surgery is contemplated; and
      3. Ultrasonography for detection of internal derangements of the temporomandibular joint; and
      4. Computed tomography (CT) or magnetic resonance imaging (MRI) only when used in conjunction with anticipated surgical management.
    2. Non-Surgical Management

      Medically necessary comprehensive non-surgical management of TMJ/TMD includes all of the following, unless contraindicated:

      1. Reversible Intra-Oral Appliances

        (i.e., removable occlusal orthopedic appliances-orthotics, stabilization appliances, occlusal splints, bite appliances/planes/splints, mandibular occlusal repositioning appliances [MORAs])

        Reversible intra-oral appliances may be considered medically necessary in selected cases only when there is evidence of clinically significant masticatory impairment with documented pain and/or loss of function.  Prolonged (greater than 6 months) application of TMD/J intra-oral appliances is not considered medically necessary unless, upon individual case review, documentation is provided that supports prolonged intra-oral appliance use.  Note: Appliances for bruxism are typically excluded under Aetna medical plans (please check benefit plan descriptions), but may be covered under dental plans.  Only 1 oral splint or appliance is considered medically necessary for TMD/TMJ therapy. 

        For plans that cover intra-oral appliances, adjustments of intra-oral appliances performed within 6 months of initial appliance therapy are considered medically necessary; while adjustments performed after 6 months are subject to review to determine necessity and appropriateness.  More than 4 adjustments or adjustments that are done more than 1 year after placement of the initial appliance are subject to review.  Note: Replacement of a lost, missing or stolen intra-oral appliance is not covered; while replacement (for other reasons) or repair is subject to review to determine necessity and appropriateness.

        Note:  Intra-oral appliances for the treatment of headaches or trigeminal neuralgia are considered experimental, investigational, or unproven, as there is insufficient data on the effectiveness of this therapy.  See CPB 0688 - Intra-oral Appliances for Headaches and Trigeminal Neuralgia.

      2. Physical Therapy

        Aetna considers physical therapy to be a medically necessary conservative method of TMD/TMJ treatment.  Therapy may include repetitive active or passive jaw exercises, thermal modalities (e.g., hot or cold packs), manipulation, vapor coolant spray-and-stretch technique, and electro-galvanic stimulation. See CPB 0325 - Physical Therapy for medical necessity criteria and documentation requirements for physical therapy. For manipulation under anesthesia for TMD/TMJ, see CPB 0204 - Manipulation Under General Anesthesia.

      3. Pharmacological Management

        Aetna considers non-opiate analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) medically necessary for mild-to-moderate inflammatory conditions and pain.  Low-dosage tricyclic antidepressants (e.g., amitriptyline) are considered medically necessary for treatment of chronic pain, sleep disturbance and nocturnal bruxism.  Adjuvant pharmacologic therapies, including anticonvulsants, membrane stabilizers, and sympatholytic agents, are considered medically necessary for unremitting TMJ pain.  Opiate analgesics, corticosteroids, anxiolytics, and muscle relaxants are considered medically necessary in refractory pain.

      4. Relaxation Therapy and Cognitive Behavioral Therapy (CBT)

        Aetna considers relaxation therapy, electromyographic biofeedback and cognitive behavioral therapy medically necessary for treatment of TMJ/TMD.

        Aetna considers relaxation therapy, electromyographic biofeedback, and cognitive behavioral therapy medically necessary in chronic headaches and insomnia, which are frequently associated with TMD/TMJ conditions.  The above therapies may be considered medically necessary in treating these conditions as well.  Treatment in multi-disciplinary pain centers may be considered medically necessary in those few individuals who have been unresponsive to less comprehensive interventions. See CPB 0237 - Chronic Pain Programs.

      5. Acupuncture and Trigger Point Injections

        (Note: some plans limit coverage of acupuncture only when used in lieu of surgical anesthesia.  Please check plan benefit descriptions for details. See CPB 0135 - Acupuncture).  Aetna considers acupuncture and trigger point injections medically necessary for persons with temporomandibular pain.  For acute pain, generally 2 visits per week for 2 weeks are considered medically necessary.  Additional treatment is considered medically necessary when pain persists and further improvement is expected.

      6. Manipulation for reduction of fracture or dislocation of the TMJ

        Aetna considers manipulation medically necessary for reduction of fracture or dislocation of the temporomandibular joint.

      7. Intra-Articular Corticosteroid Injection

        Aetna considers intra-articular corticosteroid injection medically necessary for the treatment of TMJ disorder.

    3. Surgical Procedures

      Medically necessary surgical procedures for TMJ/TMD include therapeutic arthroscopy, arthrocentesis, condylotomy/eminectomy, modified condylotomy, arthroplasty, and joint reconstruction using autogenous or alloplastic materials. In general, the least invasive appropriate surgical treatments should be attempted prior to progression to more complicated surgeries. Note: All TMJ surgical precertification requests or claims are reviewed by Aetna's Oral and Maxillofacial Surgery (OMS) Patient Management Unit.

      TMJ surgery may be considered medically necessary when the following general medical necessity criteria are met, and procedure specific criteria below are met.

      1. General medical necessity criteria for TMJ surgery

        TMJ surgery may be considered medically necessary when the following general medical necessity criteria are met, and procedure specific criteria below are met:

        1. There is conclusive evidence that severe pain or functional disability is produced by an intra-capsular condition; and
        2. The intracapsular condition is confirmed by magnetic resonance imaging (MRI), computed tomography or other imaging; and
        3. The condition has not responded to nonsurgical management, and surgery is considered to be the only remaining option. Nonsurgical management should include three or more months of the following, where appropriate:

          1. professional physical therapy,
          2. pharmacological therapy,
          3. behavioral therapy (such as cognitive behavioral therapy or relaxation therapy),
          4. manipulation (for reduction of dislocation or fracture of the TMJ), and
          5. reversible intra-oral appliances (unless the member is unable to open mouth wide enough).

        In certain cases (e.g., bony ankylosis and failed TMJ total joint prosthetic implants) that require immediate surgical intervention, surgery may be considered medically necessary without prior non-surgical management.

        Note: All requests for surgery must include documentation that all medically appropriate non-surgical therapies noted above have been exhausted. Patients with chronic head and neck pain may be candidates for chronic pain assessment.

      2. Surgical procedure-specific criteria

        TMJ surgery may be considered medically necessary when the following procedure-specific criteria are met in persons who meet general criteria for TMJ surgery above:

        1. Arthrocentesis with insufflation, lysis, and lavage is considered medically necessary when imaging and clinical examination reveal anchored disc phenomenon, anterior disc displacement without reduction and without effusion, osteoarthritis without fibrosis or loose bone particles, open lock, or hemarthrosis. Note: For purposes of this policy, arthrocentesis for TMJ internal derangement is defined as the insertion of two separate single- needle portals or a single double- needle portal for input and output of fluids.  The process includes insufflation of the joint space, lavage, manipulation of the mandible for the purpose of lysis of adhesions, and the elective infusion of steroids.
        2. Therapeutic arthroscopy is considered medically necessary when MRI or other imaging confirms the presence of adhesions, fibrosis, degenerative joint disease, or internal derangement of the disc that requires internal modification.
        3. Open surgical procedures including, but not limited to meniscus or disc repositioning or plication, disc repair, and disc removal with or without replacement are considered medically necessary when TMJ dysfunction is the result of congenital anomalies, trauma, or disease in patients who have failed nonsurgical management.
        4. Arthroplasty or arthrotomy includes: a) disk repair procedures; b) diskectomy with or without replacement; and c) articular surface recontouring (condylectomy and eminectomy or eminoplasty). Arthroplasty or arthrotomy is considered medically necessary when MRI or other imaging confirms the presence of any of the following: 
           
          1. Osteoarthritis or osteoarthrosis; or
          2. Severe disc displacement associated with degenerative changes or perforation; or
          3. Scarring that is severe and often the result of old injury or prior procedure
        5. Joint replacement with an FDA-approved prosthesis (including the TMJ Concepts prosthesis, the Christensen TMJ Fossa-Eminence Prosthesis System (partial TMJ prosthesis), the Christensen TMJ Fossa-Eminence/Condylar Prosthesis System (Christensen total joint prosthesis), or the W. Lorenz TMJ prosthesis) is considered medically necessary when used as a “salvage device” for treatment of end-stage TMJ disease, when conservative management and other surgical treatment has been unsuccessful, and MRI or other imaging documents one or more of the following:

          1. Temporal bone that no longer provides a smooth articular fossa; or
          2. Damaged condyles that are no longer ball-shaped; or
          3. Persistent, stable inflammatory arthritis that is not responsive to other modalities of treatment; or
          4. Recurrent fibrous or bony ankylosis that is not responsive to other modalities of treatment; or
          5. Loss of mandibular condylar height and/or occlusal relationship due to trauma, resorption, pathological lesion or congenital anomaly; or
          6. Failed autologous bone graft or alloplastic reconstruction effort.
        6. Autogenous grafts (e.g., costochondral, cartilage, dermal, fat, fascial and other autogenous graft materials) may be considered medically necessary upon individual case review. Autologous costochondral grafts are considered medically necessary when:

          1. General medical necessity criteria for joint replacement ( II.D.) are met; or
          2. When there is congenital absence or deformity of the joint; or
          3. For surgical reconstruction post head and neck tumor resection.
  2. Policy Limitations and Exclusions

    Notes Some Aetna HMO plans exclude coverage for treatment of temporomandibular disorders (TMD) and temporomandibular joint (TMJ) dysfunction, and may also exclude coverage for other services described in this bulletin (e.g., non-surgical management). The plan determines the scope of coverage.  Please check benefit plan descriptions for details.

  3. Experimental, Investigational, or Unproven

    The following are considered experimental, investigational, or unproven for TMD/TMJ dysfunction because of insufficient evidence of effectiveness:

    1. Diagnostic Procedures 

      1. Artificial intelligence technologies for the diagnosis of TMD
      2. Cephalometric or lateral skull x-rays 
      3. Computerized mandibular scan/kinesiography/electrogathograph/jaw tracking
      4. Diagnostic study models
      5. Electromyography (EMG), surface EMG (see CPB 0112 - Surface Scanning and Macro Electromyography)
      6. Electronic registration (Myomonitor)
      7. Genetic testing
      8. Joint vibration analysis
      9. Measurements of circulating omentin-1 levels
      10. Muscle testing/range of motion measurements (incidental to examination)
      11. Neuromuscular junction testing
      12. Salivary stress biomarkers (e.g., alpha-amylase and cortisol levels)
      13. Somatosensory testing
      14. Sonogram (ultrasonic Doppler auscultation)
      15. Standard dental radiographic procedures
      16. Thermography (see CPB 0029 - Thermography).
    2. Non-Surgical Treatments

      1. Autologous blood injection
      2. Bio-oxidative ozone therapy
      3. Botulinum toxin (type A or type B) (however, botulinum toxin type A is considered medically necessary for jaw-closing oromandibular dystonia - see CPB 0113 - Botulinum Toxin)
      4. Continuous passive motion (see CPB 0010 - Continuous Passive Motion (CPM) Machines)
      5. Cranial (craniosacral) manipulation (see CPB 0388 - Complementary and Alternative Medicine)
      6. Cryo-analgesia
      7. Dental restorations/prostheses (see CPB 0082 - Dental Services and Oral and Maxillofacial Surgery: Coverage Under Medical Plans)
      8. Dextrose prolotherapy
      9. Diathermy, infrared, and ultrasound treatments
      10. Dry needling
      11. Gallium aluminum arsenide laser therapy for the treatment of TMD with myofascial pain
      12. Hydrotherapy (immersion therapy, whirlpool baths)
      13. Hypnosis/relaxation therapy
      14. Injection of plasma rich in growth factors
      15. Iontophoresis (see CPB 0229 - Iontophoresis)
      16. Intra-articular injection of analgesics
      17. Intra-articular injection of hyaluronic acid (viscosupplementation)
      18. Intra-articular injection of platelet-rich plasma
      19. Intra-articular injections of rituximab
      20. Intraoral appliances for headache or trigeminal neuralgia (see CPB 0688 - Intra-oral Appliances for Headache and Trigeminal Neuralgia)
      21. Irreversible occlusion therapy aimed at modification of the occlusion itself through alteration of the tooth structure or jaw position
      22. Ketamine (local/intra-articular administration)
      23. Laser capsulorrhaphy
      24. Magnetic neurostimulator
      25. Manual therapy
      26. MIRO therapy
      27. Myofunctional therapy
      28. Myomonitor treatment (J-4, BNS-40, Bio-TENS)
      29. Neuromuscular re-education
      30. Orthodontic/bite adjustment services and orthodontic fixed appliances (see CPB 0095 - Orthognathic Surgery; and CPB 0082 - Dental Services and Oral and Maxillofacial Surgery: Coverage Under Medical Plans)
      31. Permanent mandibular repositioning (e.g., equilibration, orthodontics)
      32. Photo-biomodulation for the treatment of TMD and TMJ dysfunction
      33. Phototherapy (e.g., low-level (cold) laser therapy (LLLT) and light-emitting diode (LED) therapy) see CPB 0363 - Cold Laser and High-Power Laser Therapies)
      34. Platelet-rich fibrin for the treatment of TMD and TMJ dysfunction
      35. Propranolol
      36. Prophylactic management of TMJ disorder, including occlusal adjustment
      37. Radiofrequency generator thermolysis (see also CPB 0400 - Ernest or Eagle's Syndrome (Stylomandibular Ligament Pain): Treatment with Radiofrequency Thermoneurolysis)
      38. Sclerotherapy
      39. Stem cell therapy
      40. Therabite Jaw Motion Rehabilitation System (see CPB 0412 - Therabite Jaw Motion Rehabilitation System)
      41. Transcranial direct current stimulation
      42. Transcutaneous electrical nerve stimulation (TENS) (see CPB 0011 - Electrical Stimulation for Pain)
    3. Surgical Treatments

      1. Disc plication other than as medically necessary above
      2. Orthognathic surgery (see CPB 0095 - Orthognathic Surgery)
      3. Permanent mandibular repositioning (e.g., full-mouth reconstruction)
      4. Treatment of alveolar cavitational osteopathosis (see CPB 0642 - Neuralgia Inducing Cavitational Osteonecrosis (NICO) and Ultrasonograph Bone Densitometer to Detect NICO)
  4. Related Policies

    1. CPB 0004 - Obstructive Sleep Apnea in Adults
    2. CPB 0010 - Continuous Passive Motion (CPM) Machines
    3. CPB 0011 - Electrical Stimulation for Pain
    4. CPB 0029 - Thermography
    5. CPB 0082 - Dental Services and Oral and Maxillofacial Surgery: Coverage Under Medical Plans
    6. CPB 0095 - Orthognathic Surgery
    7. CPB 0112 - Surface Scanning and Macro Electromyography
    8. CPB 0113 - Botulinum Toxin
    9. CPB 0135 - Acupuncture
    10. CPB 0204 - Manipulation Under General Anesthesia
    11. CPB 0229 - Iontophoresis
    12. CPB 0237 - Chronic Pain Programs
    13. CPB 0325 - Physical Therapy
    14. CPB 0363 - Cold Laser and High-Power Laser Therapies
    15. CPB 0388 - Complementary and Alternative Medicine
    16. CPB 0400 - Ernest or Eagle's Syndrome (Stylomandibular Ligament Pain): Treatment with Radiofrequency Thermoneurolysis
    17. CPB 0412 - Therabite Jaw Motion Rehabilitation System
    18. CPB 0642 - Neuralgia Inducing Cavitational Osteonecrosis (NICO) and Ultrasonograph Bone Densitometer to Detect NICO
    19. CPB 0688 - Intra-oral Appliances for Headaches and Trigeminal Neuralgia

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

CPT codes covered if selection criteria are met:

20552 Injection(s); single or multiple trigger point(s), 1 or 2 muscle(s)
20553     single or multiple trigger point(s), 3 or more muscles
20605 Arthrocentesis, aspiration and/or injection, intermediate joint or bursa (eg, temporomandibular, acromioclavicular, wrist, elbow or ankle, olecranon bursa); without ultrasound guidance [not covered for viscosupplementation injection] [not covered for intra-articular injections of rituximab] [not covered for Intra-articular injection of analgesic]
20910 Cartilage graft; costochondral [autologous]
21010 Arthrotomy, tempomandibular joint
21050 Condylectomy, tempomandibular joint (separate procedure)
21060 Meniscectomy, partial or complete, tempomandibular joint (separate procedure)
21070 Coronoidectomy (separate procedure)
21073 Manipulation of temporomandibular joint(s) (TMJ), therapeutic, requiring an anesthesia service (ie, general or monitored anesthesia care)
21076 Impression and custom preparation; surgical obturator prosthesis
21079     interim obturator prosthesis
21080     definitive obturator prosthesis
21081     mandibular resection prosthesis
21085     oral surgical splint
21110 Application of interdental fixation device for conditions other than fracture or dislocation, includes removal
21193 Reconstruction of mandibular rami, horizontal, vertical, C, or L osteotomy; without bone graft
21198 Osteotomy, mandible, segmental;
21240 Arthroplasty, temporomandibular joint, with or without autograft (includes obtaining graft)
21242 Arthroplasty, temporomandibular joint, with allograft
21243 Arthroplasty, temporomandibular joint, with prosthetic joint replacement
21255 Reconstruction of zygomatic arch and glenoid fossa with bone and cartilage (includes obtaining autografts)
21440 Closed treatment of mandibular or maxillary alveolar ridge fracture (separate procedure)
21445 Open treatment of mandibular or maxillary alveolar ridge fracture (separate procedure)
21450 Closed treatment of mandibular fracture; without manipulation
21451     with manipulation
21452 Percutaneous treatment of mandibular fracture; with external fixation
21453 Closed treatment of mandibular fracture with interdental fixation
21454 Open treatment of mandibular fracture with external fixation
21461 Open treatment of mandibular fracture; without interdental fixation
21462     with interdental fixation
21465 Open treatment of mandibular condylar fracture
21470 Open treatment of complicated mandibular fracture by multiple surgical approaches including internal fixation, interdental fixation, and/or wiring of dentures or splints
21480 Closed treatment of temporomandibular dislocation; initial or subsequent
21485     complicated (e.g., recurrent requiring intermaxillary fixation or splinting), initial or subsequent
21490 Open treatment of temporomandibular dislocation
21497 Interdental wiring, for condition other than fracture
29800 Arthroscopy, temporomandibular joint, diagnostic, with or without synovial biopsy (separate procedure)
29804 Arthroscopy, temporomandibular joint, surgical
70355 Orthopantogram (eg, panoramic x-ray)
76536 Ultrasound, soft tissues of head and neck (eg, thyroid, parathyroid, parotid), real time with image documentation [ultrasonography of temporomandibular joints]
90832 - 90840 Psychotherapy
90901 Biofeedback training by any modality
97010 Application of a modality to 1 or more areas; hot or cold packs
97110 Therapeutic procedure, one or more areas, each 15 minutes; therapeutic exercises to develop strength and endurance, range of motion and flexibility
97124     massage, including effleurage, petrissage and/or tapotement (stroking, compression, percussion)
97140 Manual therapy techniques (e.g., mobilization/manipulation, manual lymphatic drainage, manual traction), one or more regions, each 15 minutes
97530 Therapeutic activities, direct (one-on-one) patient contact by the provider (use of dynamic activities to improve functional performance), each 15 minutes
97810 Acupuncture, 1 or more needles; without electrical stimulation, initial 15 minutes of personal one-on-one contact with the patient
+ 97811     without electrical stimulation, each additional 15 minutes of personal one-on-one contact with the patient, with re-insertion of needle(s) (List separately in addition to primary procedure)
97813     with electrical stimulation, initial 15 minutes of personal one-on-one contact with the patient
+ 97814     with electrical stimulation, each additional 15 minutes of personal one-on-one contact with the patient, with re-insertion of needle(s) (List separately in addition to primary procedure)

CPT codes not covered for indications listed in the CPB:

Bio-oxidative ozone therapy, Magnetic neurostimulator, MIRO therapy, TMJ laser capsulorrhaphy, TMJ sclerotherapy, TMJ discplication, Cryo-analgesia, Artificial intelligence technologies, Gallium aluminum arsenide laser therapy, Photo-biomodulation - no specific code
0232T Injection(s), platelet rich plasma, any site, including image guidance, harvesting and preparation when performed
0481T Injection(s), autologous white blood cell concentrate (autologous protein solution), any site, including image guidance, harvesting and preparation, when performed
20560 Needle insertion(s) without injection(s); 1 or 2 muscle(s)
20561     3 or more muscles
21120 - 21123 Genioplasty
21125 - 21127 Augmentation mandibular body or angle
21141 - 21147 Reconstruction midface, Lefort I
21150 - 21151 Reconstruction midface, Lefort II
21154 - 21155 Reconstruction midface, Lefort III (extracranial), any type, requiring bone grafts (includes obtaining autografts)
21159 - 21160 Reconstruction midface, Lefort III (extra and intracranial) with forehead advancement (e.g., mono bloc), requiring bone grafts (includes obtaining autografts)
21194 Reconstruction of mandibular rami, horizontal, vertical, C, or L osteotomy; with bone graft (includes obtaining graft)
21195 - 21196 Reconstruction of mandibular rami and/or body, sagittal split
21199 Osteotomy, mandible, segmental; with genioglossus advancement
21206 Osteotomy, maxilla, segmental (e.g., Wassmund or Schuchard)
21208 - 21209 Osteoplasty, facial bones
21247 Reconstruction of mandibular condyle with bone and cartilage autografts (includes obtaining grafts) (e.g., for hemifacial microsomia)
21248 - 21249 Reconstruction of mandible or maxilla, endosteal implant (e.g., blade, cylinder)
38205 Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic
38206     autologous
38230 Bone marrow harvesting for transplantation; allogenic
38232     autologous
38240 Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor
38241     autologous transplantation
38242 Allogeneic lymphocyte infusions
70300 Radiologic examination, teeth; single view
70310     partial examination, less than full mouth
70320     complete, full mouth
70487 Computerized tomography, maxillofacial area; with contrast material(s)
70488     without contrast material, followed by contrast material(s) and further sections
77077 Joint survey, single view, 2 or more joints (specify) [joint vibration analysis for TMJ]
90867 Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; initial, including cortical mapping, motor threshold determination, delivery and management
90868     subsequent delivery and management, per session
90869     subsequent motor threshold re-determination with delivery and management
90880 Hypnotherapy
95867 Needle electromyography; cranial nerve supplied muscle(s), unilateral
95868     cranial nerve supplied muscles, bilateral
95887 Needle electromyography, non-extremity (cranial nerve supplied or axial) muscle(s) done with nerve conduction, amplitude and latency/velocity study (List separately in addition to code for primary procedure)
95937 Neuromuscular junction testing (repetitive stimulation, paired stimuli), each nerve, any one method
96900 Actinotherapy (ultraviolet light)
96910 Photochemotherapy; tar and ultraviolet B (Goeckerman treatment) or petrolatum and ultraviolet B
96912 Photochemotherapy; psoralens and ultraviolet A (PUVA)
96913 Photochemotherapy (Goeckerman and/or PUVA) for severe photoresponsive dermatoses requiring at least 4-8 hours of care under direct supervision of the physician (includes application of medication and dressings)
97014 Application of a modality to 1 or more areas; electrical stimulation (unattended)
97024     diathermy (e.g., microwave)
97026     infrared
97028     ultraviolet
97032 Application of a modality to one or more areas; electrical stimulation (manual), each 15 minutes
97033     iontophoresis, each 15 minutes
97035     ultrasound, each 15 minutes
97036     Hubbard tank, each 15 minutes
97129 Therapeutic interventions that focus on cognitive function (eg, attention, memory, reasoning, executive function, problem solving, and/or pragmatic functioning) and compensatory strategies to manage the performance of an activity (eg, managing time or schedules, initiating, organizing, and sequencing tasks), direct (one-on-one) patient contact; initial 15 minutes
+97130     each additional 15 minutes (List separately in addition to code for primary procedure)
97750 Physical performance test or measurement (e.g., musculoskeletal, functional capacity), with written report, each 15 minutes

Other CPT codes related to the CPB:

70328 Radiologic examination, temporomandibular joint, open and closed mouth; unilateral [covered only when used in conjunction with anticipated surgical management]
70330     bilateral [covered only when used in conjunction with anticipated surgical management]
70332 Temporomandibular joint arthrography, radiological supervision and interpretation
70336 Magnetic resonance (e.g., proton) imaging, temporomandibular joint(s) [covered only when used in conjunction with anticipated surgical management]
70486 Computerized tomography, maxillofacial area; without contrast material [covered only when used in conjunction with anticipated surgical management]
70540 Magnetic resonance (e.g., proton) imaging, orbit, face, and/or neck; without contrast material(s)
70542     with contrast material(s)
70543     without contrast material(s), followed by contrast material(s) and further sequences

HCPCS codes covered if selection criteria are met:

D0320 Temporomandibular joint arthrogram, including injection
D0321 Other temporomandibular joint films, by report
D0322 Tomographic survey
D0330 Panoramic radiographic image
D0340 Cephalometric film
D0701 Panoramic radiographic image – image capture only
D0702 2-D cephalometric radiographic image – image capture only
D5931 - D5933, D5936 Obturator prostheses
D5934 Mandibular resection prosthesis with guide flange
D5982 Surgical stent
D5988 Surgical splint
D7630 Mandible, open reduction (teeth immobilized, if present)
D7640 Mandible, closed reduction (teeth immobilized, if present)
D7730 Mandible, open reduction
D7740 Mandible, closed reduction
D7810 - D7880 Reduction of dislocation and management of other temporomandibular joint dysfunctions
D7881 Occlusal orthotic device adjustment
D7993 Surgical placement of craniofacial implant – extra oral
D9130 Temporomandibular joint dysfunction - non-invasive physical therapies
D9943 - D9946 Occlusal guard
D9951 - D9952 Occlusal adjustment, limited/complete
E0746 Electromyography (EMG), biofeedback device

HCPCS codes not covered for indications listed in the CPB:

A4556 Electrodes (e.g., apnea monitor), per pair
A4557 Lead wires (e.g., apnea monitor), per pair
A4558 Conductive gel or paste, for use with electrical device (e.g., TENS, NMES), per oz.
A4595 Electrical stimulator supplies, 2 lead, per month, (e.g., TENS, NMES)
D5110 - D5899 Prosthodontics (removable)
D6210 - D6999 Prosthodontics (fixed)
D7899 Unspecified TMD therapy, by report
D7940 Osteoplasty, for orthognathic deformities
D7941 Osteotomy - mandibular rami
D7943 Osteotomy - mandibular rami with bone graft; includes obtaining the graft
D7944 Osteotomy - segmented or subapical
D7945 Osteotomy, body of mandible
D7946 Lefort I (maxilla, total)
D7947 Lefort I (maxilla, segmented)
D7948 Lefort II or Lefort III (osteoplasty of facial bones for midfce hypoplasia or retrusion), without bone graft
D7949 Lefort II or Lefort III, with bone graft
D7950 Osseous, osteoperiosteal, or cartilage graft of the mandible or maxilla, autogenous or nonautogenous, by report
D7951 Sinus augmentation with bone or bone substitutes
D7953 Bone replacement graft for ridge preservation - per site
D7955 Repair of maxillofacial soft and/or hard tissue defect
E0720 Transcutaneous electrical nerve stimulation (TENS) device, 2 lead, localized stimulation
E0730 Transcutaneous electrical nerve stimulation (TENS) device, 4 or more leads, for multiple nerve stimulation
E0745 Neuromuscular stimulator, electronic shock unit
J0585 Botulinum toxin type A, per unit [Botox]
J0586 Injection, Abobotulinumtoxina, 5 units [Dysport]
J0587 Injection, rimabotulinumtoxinB, 100 units
J0588 Injection, incobotulinumtoxinA, 1 unit [Xeomin]
J1800 Injection, propranolol hcl, up to 1 mg
J7321 Hyaluronan or derivative, Hyalgan or Supartz, for intra-articular injection, per dose [knee only - see selection criteria]
J7323 Hyaluronan or derivative, Euflexxa, for intra-articular injection, per dose [knee only - see selection criteria]
J7324 Hyaluronan or derivative, Orthovisc, for intra-articular injection, per dose [knee only - see selection criteria]
J7325 Hyaluronan or derivative, Synvisc, or Synvisc-One for intra-articular injection, per dose [knee only - see selection criteria]
J9312 Injection, rituximab, 10 mg
M0076 Prolotherapy

Other HCPCS codes related to the CPB:

J0702 Injection, betamethasone acetate 3 mg and betamethasone sodium phosphate 3 mg
J1020 Injection, methylprednisolone acetate, 20 mg
J1030 Injection, methylprednisolone acetate, 40 mg
J1040 Injection, methylprednisolone acetate, 80 mg
J1094 Injection, dexamethasone acetate, 1 mg
J1100 Injection, dexamethasone sodium phosphate, 1 mg
J1700 Injection, hydrocortisone acetate, up to 25 mg
J1710 Injection, hydrocortisone sodium phosphate, up to 50 mg
J1720 Injection, hydrocortisone sodium succinate, up to 100 mg
J2650 Injection, prednisolone acetate, up to 1 ml
J2920 Injection, methylprednisolone sodium succinate, up to 40 mg
J2930 Injection, methylprednisolone sodium succinate, up to 125 mg
J3300 Injection, triamcinolone acetonide, preservative free, 1 mg
J3301 Injection, triamcinolone acetonide, not otherwise specified, 10 mg
J3302 Injection, triamcinolone diacetate, per 5 mg
J3303 Injection, triamcinolone hexacetonide, per 5 mg

ICD-10 codes covered if selection criteria are met:

M26.601 - M26.69 Temporomandibular joint disorders
S02.400+ - S02.413+
S02.42x+
S02.600+ - S02.69x+
Fracture of mandible, closed or open, or malar and maxillary bones closed or open
S03.00x+ - S03.02x+ Dislocation of jaw (closed or open)

Background

Although the precise etiology of temporomandibular joint (TMJ) syndrome and temporomandibular joint disorder (TMD) has not yet been identified, these conditions are believed to be the result of either "macro" or "micro" trauma affecting the joint and/or the associated facial musculature.  Macro-trauma is usually historically obvious (e.g., acute joint overload), and there is generally a documented history of direct trauma to the TMJ.  Micro-trauma is a chronic and insidious process, multi-factorial in presentation, and commonly associated with para-functional habits, stress and anxiety, sleep disorders, dysfunctional occlusion, and various myofascial conditions (e.g., fibromyalgia).

The etiology of temporomandibular disorders are intracapsular or extracapsular.  Intracapsular abnormalities consist of internal derangements, including anterior disc displacement with or without reduction, disc perforation or fragmentation leading to degenerative joint disease, rheumatoid arthritis, synovitis, and neoplasia.  Extracapsular abnormalities consist of myalgia or myospasm which may be related to trauma or parafunctional habits such as bruxism, tooth pain, or postural abnormalities.  

The diagnosis of TMD is largely based upon the symptoms of pain and signs of TMD (e.g., joint sounds, variations from ideal disc position, clicking).  These signs may also be found in large segments of the general population without evidence of impairment or dysfunction.  According to available literature, specialized radiological studies (e.g., cephalometric x-rays, tomograms, submental vertex radiographs) are not medically necessary in evaluating persons with TMD unless surgery is being considered.

The extent of internal derangements is often determined by magnetic resonance imaging (MRI).  MRI is a useful for assessing disc morphology, disc fragmentation, and the disc-condylar relationship, especially where the patient is in a closed lock with a limited oral opening.  Limchaichana et al (2006) assessed the evidence for the effectiveness of MRI in the diagnosis of disk position and configuration, disk perforation, joint effusion, and osseous and bone marrow changes in the TMJ.  Two reviewers evaluated the level of evidence of relevant publications as high, moderate, or low.  Based on this, the evidence grade for diagnostic efficacy was rated as strong, moderately strong, limited, or insufficient.  The literature search yielded 494 titles, of which 22 were relevant.  No publication had a high level of evidence, and 12 had moderate and 10 low levels of evidence.  The evidence grade for diagnostic efficacy expressed as sensitivity, specificity, and predictive values was insufficient.  The authors concluded that evidence for the effectiveness of MRI is insufficient; and it emphasizes the need for high-quality studies on the diagnostic efficacy of MRI, incorporating accepted methodological criteria.

Therapy of TMD varies considerably according to the particular training, discipline and experience of the clinician.  This variation in clinical practice is due, in part, to a paucity of evidence-based outcome research and lack of consensus on the appropriate management of TMD.  Scientifically valid clinical trials are lacking for the vast majority of therapies that are currently employed.  There are also no objective, generally accepted, diagnostic standards to correctly identify when a TMD is present.

The appropriate diagnosis and treatment of TMD is complicated by a high incidence of TMD/TMJ signs and symptoms that are associated with systemic disorders.  These usually represent local or regional manifestations of chronic, global, musculoskeletal pain conditions, such as fibromyalgia, systemic myofascial pain and chronic fatigue syndrome.  While an association with headaches has been identified, a causal relationship between TMD/TMJ and headaches has not been established.  These conditions occur coincidentally and may be produced by etiologic factors that are common to both.

The National Institutes of Health emphasizes the importance of 2 key words in therapy: conservative and reversible.  A growing body of literature supports non-surgical intervention for this condition.  Similar to other musculoskeletal/joint conditions, treatment is directed towards unloading the affected structures and managing the attendant discomfort.  Non-surgical therapy customarily includes occlusal appliance therapy, physical therapy, medical management, and relaxation/cognitive-behavioral therapy.  Prudence usually dictates that non-surgical therapy first be exhausted prior to any invasive therapies.  Patients with a long history of head and neck pain may be candidates for a chronic pain assessment.

The American Academy of Oral and Maxillofacial Surgeons Parameters of Care (2012) states: "Surgical intervention for internal derangement is indicated only when nonsurgical therapy has been ineffective and pain and/or dysfunction are moderate to severe.  Surgery is not indicated for asymptomatic or minimally symptomatic patients. Surgery also is not indicated for preventive reasons in patients without pain and with satisfactory function.  Pretreatment therapeutic goals are determined individually for each patient."

Appliance (splint) therapy has been shown to be beneficial for TMD.  These devices represent the most common and effective TMD/TMJ therapy that is routinely provided by dentists, even though the physiologic mechanism of the treatment response is not completely understood.  Splint design and usage are different depending upon whether the etiology is intracapsular or extracapsular.  For extracapsular problems, a night guard or bite plain appliance worn at night may help.  For intracapsular problems, the appliance needs to be worn through the entire day and night, except at meal times for a trial period of at least 2 to 3 months.  Appliance therapy would not be indicated for patients who are unable to open their mouth wide enough to obtain the impressions of dental arches that are necessary for making a dental model for a custom made appliance.

Physical therapy is an established conservative method of TMD/TMJ treatment.  As is the case with physical therapy for most other medical conditions, scientific evidence of therapeutic benefit from physical therapy in TMJ/TMD is limited.  Therapy may include repetitive active or passive jaw exercises, thermal modalities, manipulation, vapor coolant spray-and-stretch technique, and electro-galvanic stimulation.

Initial medical management of TMD/TMJ conditions may include pharmaceutical therapy, similar to other acute and chronic orthopedic and musculoskeletal conditions.  Non-opiate analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective for mild-to-moderate inflammatory conditions and pain.  Low-dosage tricyclic anti-depressants (e.g., amitriptyline) are have been used successfully in the treatment of chronic pain, sleep disturbance and nocturnal bruxism.  Adjuvant pharmacologic therapies, including anticonvulsants, membrane stabilizers, and sympatholytic agents, may be useful for unremitting TMJ pain.  Opiate analgesics, corticosteroids, anxiolytics, and muscle relaxants are also used in refractory pain.

There is strong evidence of effectiveness for the relaxation class of techniques in reducing chronic pain associated with a variety of medical conditions.  See CPB 132 - Biofeedback.  The effectiveness of electromyography (EMG) biofeedback in the treatment of TMD has been evaluated in a meta-analysis of 13 studies.  Approximately 70 % of patients required no further treatment, were symptom free, or were substantially improved following EMG biofeedback therapy, compared with approximately 35 % of patients who received placebo treatments.  A synergistic response has been demonstrated when intra-oral appliance therapy is combined with biofeedback and stress management.  These results demonstrate the importance of using both dental and psychological treatments for successful intervention.  Cognitive-behavioral therapy (CBT) also has been demonstrated to improve long-term outcomes for TMD patients, as has been the case with other chronic pain disorders.  Behavior modification interventions and relaxation techniques are frequently included as a behavioral component of CBT.

Acupuncture and trigger-point injections may be used for TMD pain.  A systematic review found substantial evidence of the effectiveness of acupuncture for treatment of TMD pain.  While relatively fewer controlled studies on trigger-point injection have been conducted, trigger-point injection and dry needling of trigger points have become widely accepted.  While dry needling and trigger point injections of anesthetic appear to be equally effective, post-injection soreness from dry needling has been found to be more intense and of longer duration than experienced by patients injected with local anesthetic.

In cases involving chronic intractable pain and/or prior (including multiple) TMJ surgical procedures, caution is recommended due to the significant morbidity that may be experienced with TMJ surgical interventions.  The long-term prognosis of this therapy for intractable pain may be unfavorable, due to the neurophysiology of chronic pain disorders.  There is also evidence that the prognosis for success decreases with each additional (repeat) TMJ surgical intervention.  In such cases, the literature indicates that the most promising treatment may be admission into a multidisciplinary chronic pain treatment program.

In a review on TMD, Laudenbach and Stoopler (2003) noted that when patients do not respond to non-invasive TMD therapy, surgical procedures are considered.  Initial closed-approach, surgical options include arthrocentesis and arthroscopy of the TMJs.  These are the simplest and least invasive of all the surgical techniques.  More advanced, open-approach TMJ surgeries include disk re-positioning, diskectomy, and modified condylotomy.  Indeed, guidelines for the diagnosis and management of disorders involving the TMJ and related musculoskeletal structures that are approved by the American Society of Temporomandibular Joint Surgeons (2001) listed condylotomy (including modified condylotomy) as one of the surgical options.

In a prospective, controlled study, Hall et al (2005) compared the outcomes of 4 operations (arthroscopy, condylotomy, discectomy, and disc repositioning) used for the treatment of painful TMJ with an internal derangement.  Studies were conducted at 3 sites, and all sites used the same inclusion and exclusion criteria.  Trained, independent examiners assessed pain, diet, and range of motion before operation and 1 month and 1 year after operation.  There were statistically significant reductions in the amount of pain (p < 0.001) and daily time in pain (p < 0.001) that were similar for all 4 operations 1 month and 1 year after the procedures.  The degrees of change after each of the 4 procedures were not statistically different from each other (amount: p = 0.453 and time: p = 0.416).  Ability to chew, as measured by diet visual analog scale, was substantially improved 1 year after operation (p < 0 .001).  The degrees of change for diet at 1 year also were not different from each other (p = 0.314).  There were, however, statistically significant differences (p < 0.05) in range of motion that varied with procedure.  The authors concluded that all 4 operations were followed by marked improvements in pain and diet.  The amounts of improvement varied slightly by operation, but these differences were not statistically significant.  There were small but statistically significant differences between procedures for range of motion.

McKenna (2006) stated that the therapeutic objective of modified condylotomy is to increase joint space, providing immediate joint load reduction and reducing if not abolishing condylar interference.  The technical aspects of modified condylotomy are simple and familiar to surgeons comfortable with intraoral vertical ramus osteotomy.  Satisfactory pain relief following modified condylotomy for non-reducing disc displacement (NRDD) demonstrate that disc reduction is not a pre-requisite.  However, when disc reduction is possible, as it often is in reducing disc displacement joints or joints that have recently progressed to NRDD, the odds of pain relief, especially moderate to severe pain, are improved and lower the risk for re-operation.  Furthermore, modified condylotomy seems to favorably change the natural course of internal derangement/osteoarthrosis.

A partial TMJ prosthesis consists of a meniscectomy and placement of a metallic glenoid fossa metal prosthesis (Christensen fossa-eminence prosthesis, TMJ, Inc., Golden, CO) in place of the meniscus, such that a natural condyle articulates with a metal fossa prosthesis.  The U.S. Food and Drug Administration (FDA) Dental Products Advisory Panel reviewed clinical studies of the Christensen fossa prosthesis, and advised the FDA to approve the total prosthesis, but to not approve the partial joint prosthesis because of a lack of clinical data on its safety and effectiveness.  The information originally submitted to the FDA on the safety and effectiveness of the partial TMJ prosthesis was limited and had not been published in a peer-reviewed journal.  In an editorial, Laskin (2001), former editor-in-chief of the Journal of Oral and Maxillofacial Surgery, the official journal of the American Association of Oral and Maxillofacial Surgeons, commented on the data on the partial TMJ prosthesis presented to the FDA Dental Products Advisory Panel: “At that meeting [of the FDA Dental Products Advisory Panel where the partial TMJ prosthesis was considered] the FDA staff presentation expressed concern regarding the lack of data on the effect of the natural condyle articulating against a metal fossa, the limited number of patients with long-term follow-up, and the broad diagnosis of internal derangement as an indication for its use.  The panel expressed similar concerns about these issues, as well as the fact that the registry data provided in support of the product did not include all the patients treated and the sample size was insufficient for each of the individual indications.  They recommended clarification of the patient inclusion criteria in the clinical study, evaluation of failures and additional patient follow-up, more clearly defined indications for use of the device, and that a power analysis of the clinical data be done to place the pre-market approval in an approvable form.  However, despite these criticisms, and the panel’s opinion that adequate safety and effectiveness data for the given surgical indications were lacking, the device was approved by the FDA for distribution in February 2001”.

Laskin (2001) concluded that “there are insufficient data” to answer questions about the safety and effectiveness of the partial TMJ prosthesis.  “For example, how reliable are clinical data based on a registry that did not include all patients treated with the device, in which there was a very small number of total patients with serial data and even smaller numbers in each diagnostic subcategory, and where in 1 group of 97 patients with a diagnosis of internal derangement and/or inflammatory arthritis, only 30 % (12 subjects) had a follow-up of 3 or more years and 70 % were either lost to follow-up, withdrawn, or potentially lost to follow-up.  How can one make an informed decision with such information?”

The manufacturer subsequently submitted a post-approval study to the FDA on the long-term follow-up of patients with a variety of TMJ conditions treated with the partial TMJ prosthesis (Christensen, 2008).  A total of 145 subjects (228 joints) were evaluated immediately before surgery and at regular intervals after surgery for up to 3 years.  Success was measured as improvement of function and decrease in pain as measured on a visual analog scale (VAS), as well as improved incisor opening as measured with a Therabite Scale.  Subjects showed a 4.9-cm reduction of pain on a 10-cm VAS scale and a 5.0-cm reduction in diet restriction at 36 months.  Subjects who were admitted with an inter-incisal opening of less than or equal to 15 mm showed a 19.4 mm average improvement at 18 months and 17.4 mm average improvement at 36 months.  The manufacturer reported that 4.1 % (6 subjects) of partial joint replacement subjects experienced device-related events, a percentage that was not significantly different than the percentage of device-related events reported with total joint replacement subjects (11.5 %).  Limitations of the post-approval study were similar to those of the initial study submitted for FDA approval. In particular, less than half (44 %) of the 145 subjects enrolled in the study had pain, diet restriction, and incisal opening data through three years (36 months).

The manufacturer also submitted a post-approval study to the FDA on the long-term followup of patients with a variety of TMJ conditions who were treated with the total TMJ prosthesis (Christensen, 2008).  A total of 78 subjects (127 joints) were evaluated immediately before surgery and at regular intervals after surgery for up to 3 years.  Subjects showed a 4.9 cm reduction of pain and a 5.9 cm diet restriction at 36 months.  Subjects who were admitted with an interincisal opening of less than or equal to 15 mm showed a 16.8 mm average improvement at 18 months and 18.0 mm average improvement at 36 months.  Nine subjects (11.5 %) of total joint replacement subjects experienced device-related events.  Follow-up was incomplete, as just over half (54 %) of subjects had pain data and diet restriction data (54 % and 57 %, respectively) at 36 months, and half (50 %) of subjects with reduced inter-incisal openings had incisal opening data at 36 months.

An evaluation study has reported better post-surgical outcomes with the TMJ Concepts total joint prosthesis than the Christensen total joint prosthesis.  Wolford et al (2003) reported the results of a study comparing the Christensen total joint prosthesis (TMJ Inc., Golden, CO) with the TMJ Concepts total joint prosthesis (TMJ Concepts Inc, Camarillo, CA) in 45 patients, 23 of whom were treated with the Christensen prosthesis, and 22 of whom were treated with the TMJ Concepts Prosthesis.  The investigators reported that, although subjects treated with either total joint prosthesis showed good skeletal and occlusal stability, the subjects treated with the TMJ Concepts Prosthesis had statistically significant improved outcomes compared to subjects treated with the Christensen prosthesis with respect to post-surgical incisal opening (37.3 mm versus 30.1 mm, p = 0.008), pain (decrease of 3.1 versus 1.8 on 10 point VAS score, p = 0.042), jaw function (improvement of 3.0 versus 1.2 on a 10 point scale, p = 0.008), and diet (2.0 versus 1.8 on a 10-point scale, p = 0.021).  The investigators concluded “[a]s a result of our study, it appears that [TMJ Concepts Prosthesis] provides a more biologically accepted and functional prosthesis than the [Christensen prosthesis] for the complex TMJ patient.”

In a study that examined factors to consider in joint prosthesis systems, Wolford (2006) stated that metal-on-ultra-high-molecular-weight polyethylene (UMWPE) has shown negligible wear debris histologically in the TMJ, whereas the Christensen prosthesis often demonstrates visible and histological evidence of metallosis from wear debris.  Furthermore, the author stated that to appropriately evaluate the success of the Christensen products, independent researchers (not affiliated with TMJ Implants Inc.) must perform prospective studies, because the research data provided by the company are highly suspect.

The W. Lorenz total TMJ replacement system (Walter Lorenz Surgical, Inc., Jacksonville, FL) was approved by the FDA on September 21, 2005 the FDA for the functional reconstruction of diseased and/or damaged jaw joints.  Its 2 components (mandibular condyle and glenoid fossa) are available in multiple sizes as left- and right-side specific designs.  Approved indications for the W. Lorenz TMJ replacement system include arthritic conditions such as osteoarthritis, traumatic arthritis, or rheumatoid arthritis; ankylosis including but not limited to recurrent ankylosis with excessive heterotopic bone formation; and revision procedures in which other treatments have failed (e.g., alloplastic reconstruction, autogenous grafts).  The approval was based on data from a 6-year case series study of 224 patients (329 joints), showing that patients receiving the implant reported reduced pain, improved function, an increase in maximal incisal opening, as well as satisfaction with the outcome.

The device is not intended for partial TMJ reconstruction or for use in patients susceptible to infection or having active/chronic infection, insufficient bone to support the device, an immature skeleton, or hyper-functional habits such as clenching/grinding of teeth.  An evaluation of the W. Lorenz total TMJ replacement system by the Australian Department of Health and Aging (2006) stated that the only available study on this prosthesis was the case series included in the FDA safety and effectiveness summary.  The Australian Department of Health and Aging recommended monitoring of the continual development of this technology.

Certain other total joint prostheses, such as the Vitek-Kent total joint prosthesis (Vitek Inc, Houston, TX) and silastic implants, are not considered medically necessary as they have been removed from the market due to poor biocompatibility, increased wear, fragmentation, and foreign body giant cell reaction.

For persons who already have had implant or other invasive surgery, additional surgical interventions (with the possible exception of implant removal) should be considered only with great caution, since the evidence indicates that the probability of success decreases with each additional surgical intervention.  For these persons, available evidence indicates that the most promising immediately available treatment may be a patient-centered, multidisciplinary, palliative approach.

In a pilot study, Adiels and colleagues (2005) assessed if fibromyalgia syndrome (FMS) patients with signs and symptoms of TMD refractory to conservative TMD treatment would respond positively to tactile stimulation in respect of local and/or general symptoms.  A total of 10 female patients fulfilling the inclusion criteria received such treatment once-weekly during a 10-week period.  At the end of treatment, a positive effect on both clinical signs and subjective symptoms of TMD, as well as on general body pain, was registered.  Eight out of 10 patients also perceived an improved quality of their sleep.  At follow-ups after 3 and 6 months, some relapse of both signs and symptoms could be seen, but there was still an improvement compared to the initial degree of local and general complaints.  At the 6-month follow-up, half of the patients also reported a lasting improvement of their sleep quality.  One hypothetical explanation to the positive treatment effect experienced by the tactile stimulation might be the resulting improvement of the patients' quality of sleep leading to increased serotonin levels.  The authors concluded that "the results of the present pilot study are so encouraging that they warrant an extended, controlled study".

There is insufficient evidence in the literature to support the hypothesis that orthognathic surgical correction for TMJ abnormalities such as condylar hypertrophy, status post condylar fracture, ankylosis, etc., will predictably prevent or improve a temporomandibular dysfunction.  There is no body of evidence in the peer reviewed literature to suggest that orthognathic surgery is a curative modality for internal joint derangements of the temporomandibular joints.

A systemic review on malocclusions and orthodontic treatment by the Swedish Council on Technology Assessment in Health Care (SBU, 2005) concluded that the appearance of the teeth is the patients' most important reason for seeking orthodontic treatment.  In addition, scientific evidence is insufficient for conclusions on patient satisfaction in the log-term (at least 5 years) after the conclusion of orthodontic treatment.  Furthermore, the assessment stated that scientific evidence is insufficient for conclusions on a correlation between specific untreated malocclusions and symptomatic TMJ disorders.

In a Cochrane review on orthodontics for treating TMD, Luther et al (2010) examined the effectiveness of orthodontic intervention in reducing symptoms in patients with TMD (compared with any control group receiving no treatment, placebo treatment or reassurance) and whether active orthodontic intervention leads to TMD.  The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched.  Hand-searching of orthodontic journals and other related journals was undertaken in keeping with the Cochrane Collaboration hand-searching program.  No language restrictions were applied.  Authors of any studies were identified, as were experts offering legal advice, and contacted to identify unpublished trials.  Most recent search was April 13, 2010.  All randomized controlled trials (RCTs) including quasi-randomized trials assessing orthodontic treatment for TMD were included.  Studies with adults aged equal to or above 18 years old with clinically diagnosed TMD were included.  There were no age restrictions for prevention trials provided the follow-up period extended into adulthood.  The inclusion criteria required reports to state their diagnostic criteria for TMD at the start of treatment and for participants to exhibit 2 or more of the signs and/or symptoms.  The treatment group included treatment with appliances that could induce stable orthodontic tooth movement.  Patients receiving splints for 8 to 12 weeks and studies involving surgical intervention (direct exploration/surgery of the joint and/or orthognathic surgery to correct an abnormality of the underlying skeletal pattern) were excluded.  Main outcome measures were how well the symptoms were reduced, adverse effects on oral health and quality of life.  Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in triplicate and independently by 3 review authors.  As no 2 studies compared the same treatment strategies (interventions) it was not possible to combine the results of any studies.  The searches identified 284 records from all databases.  Initial screening of the abstracts and titles by all review authors identified 55 articles that related to orthodontic treatment and TMD.  The full articles were then retrieved and of these articles only 4 demonstrated any data that might be of value with respect to TMD and orthodontics.  After further analysis of the full texts of the 4 studies identified, none of the retrieved studies met the inclusion criteria and all were excluded from this review.  The authors concluded that there are insufficient research data on which to base their clinical practice on the relationship of active orthodontic intervention and TMD.  There is an urgent need for high quality RCTs in this area of orthodontic practice.  When considering consent for patients it is essential to reflect the seemingly random development/alleviation of TMD signs and symptoms.

da Cunha et al (2008) assessed the effectiveness of low-level laser therapy (LLLT) in patients presenting with TMD.  A total of 40 patients were randomized into an experimental group (G1) or a placebo group (G2).  The treatment was carried out with an infrared laser (830 nm, 500 mW, 20s, 4J/point) at the painful points, once-weekly for 4 consecutive weeks.  Patients were evaluated before and after the treatment through a VAS and the cranio-mandibular index (CMI).  The baseline and post-therapy values of VAS and CMI were compared by the paired t-test, separately for the placebo and laser groups.  A significant difference was observed between initial and final values (p < 0.05) in both groups.  Baseline and post-therapy values of pain and CMI were compared in the therapy groups by the 2-sample t-test, yet no significant differences were observed regarding VAS and CMI (p > 0.05).  The authors concluded that after either placebo or laser therapy, pain and temporomandibular symptoms were significantly lower, although there was no significant difference between groups.  The LLLT was ineffective for the treatment of TMD, when compared to the placebo.  This is in agreement with the findings of Emshoff et al (2008) who reported that LLLT is not better than placebo in reducing TMJ pain during function (n = 52).

In a randomized, double-blinded, placebo-controlled study, Castrillon et al (2008) examined the effect of peripheral N-methyl-D-aspartate (NMDA) receptor blockade with ketamine on chronic myofascial pain in patients with TMD.  A total of 14 patients (10 women and 4 men) were recruited.  The subjects completed 2 sessions in a double-blinded randomized and placebo-controlled trial.  They received a single injection of 0.2 ml ketamine or placebo (buffered isotonic saline, 155 mmol/l) into the most painful part of the masseter muscle.  The primary outcome parameters were spontaneous pain assessed on an electronic VAS and numeric rating scale.  In addition, numeric rating scale of unpleasantness, numeric rating scale of pain relief, pressure pain threshold (PPT), pressure pain tolerance, completion of a McGill Pain Questionnaire and pain drawing areas, maximum voluntary bite force and maximum voluntary jaw opening were obtained.  Paired t-tests and analysis of variance were performed to compare the data.  There were no main effects of the treatment on the outcome parameters except for a significant effect of time for maximum voluntary bite force (analysis of variance [ANOVA]; p = 0.030) and effects of treatment, time, and interactions between treatment and time for maximum voluntary jaw opening (ANOVA; p < 0.047).  The authors concluded that these findings suggest that peripheral NMDA receptors do not play a major role in the pathophysiology of chronic myofascial TMD pain.  Although there was a minor effect of ketamine on maximum voluntary jaw opening, local administration may not be promising treatment for these patients.

Al-Saleh et al (2012) noted that although electromyography (EMG) has been used extensively in dentistry to assess masticatory muscle impairments in several conditions, especially TMD, many investigators have questioned its psychometric properties and accuracy in diagnosing TMD.  These investigators performed a systematic review to analyze the literature critically and determine the accuracy of EMG in diagnosing TMDs.  They conducted an electronic search of Medline, Embase, all Evidence-Based Medicine Reviews, Allied and Complementary Medicine, Ovid HealthSTAR and SciVerse Scopus.  They selected abstracts that fulfilled the inclusion criteria, retrieved the original articles, verified the inclusion criteria and hand searched the articles' references.  They used a methodological tool (Quality Assessment of Diagnostic Accuracy Studies [QUADAS]) to evaluate the quality of the selected articles.  The electronic database search resulted in a total of 130 articles.  The authors selected 8 articles as potentially meeting eligibility for the review.  Of these 8 articles, only 2 fulfilled the study inclusion criteria, and the authors analyzed them.  Investigators in both studies reported low sensitivity (values ranged from 0.15 to 0.40 in 1 study and a mean of 0.69 in the second study).  In addition, investigators in the 2 studies reported contradictory levels of specificity (values ranged from 0.95 to 0.98 in 1 study, and the mean value in the 2nd study was 0.67).  The likelihood ratios and predictive values were not helpful in diagnosing TMD by means of EMG.  The quality of the 2 studies was poor on the basis of the QUADAS checklist.  The authors concluded that this systematic review found no evidence to support the use of EMG for the diagnosis of TMD.

Sharma et al (2013) conducted a systematic review of papers reporting the reliability and diagnostic validity of the joint vibration analysis (JVA) for diagnosis of TMD.  A search of PubMed identified English-language publications of the reliability and diagnostic validity of the JVA.  Guidelines were adapted from applied STAndards for the Reporting of Diagnostic accuracy studies (STARD) to evaluate the publications.  A total of 15 publications were included in this review, each of which presented methodological limitations.  The authors concluded that this literature review was unable to provide evidence to support the reliability and diagnostic validity of the JVA for diagnosis of TMD.

Hypnosis / Relaxation Therapy

In a systematic review and meta-analysis, Zhang et al (2015) evaluated the effectiveness of hypnosis/relaxation therapy compared to no/minimal treatment in patients with TMD.  Studies reviewed included RCTs where investigators randomized patients with TMD or an equivalent condition to an intervention arm receiving hypnosis, relaxation training, or hypo-relaxation therapy, and a control group receiving no/minimal treatment.  The systematic search was conducted without language restrictions, in Medline, EMBASE, CENTRAL, and PsycINFO, from inception to June 30, 2014.  Studies were pooled using weighted mean differences and pooled risk ratios (RRs) for continuous outcomes and dichotomous outcomes, respectively, and their associated 95 % confidence intervals (CI).  Of 3,098 identified citations, 3 studies including 159 patients proved eligible, although none of these described their method of randomization.  The results suggested limited or no benefit of hypnosis/relaxation therapy on pain (risk difference in important pain -0.06; 95 % CI: -0.18 to 0.05; p = 0.28), or on PPTs on the skin surface over the TMJ and masticatory muscles.  Low-quality evidence suggested some benefit of hypnosis/relaxation therapy on maximal pain (mean difference on 100-mm scale = -28.33; 95 % CI: -44.67 to -11.99; p = 0.007) and active maximal mouth opening (mean difference on 100-mm scale = -2.63 mm; 95 % CI: -3.30 mm to -1.96 mm; p < 0.001) compared to no/minimal treatment.  The authors concluded that 3 RCTs were eligible for the systematic review, but they were with high risk of bias and provided low-quality evidence, suggesting that hypnosis/relaxation therapy may have a beneficial effect on maximal pain and active maximal mouth opening but not on pain and PPT.  They stated that larger RCTs with low risk of bias are needed to confirm or refute these findings and to inform other important patient outcomes.

Manual Therapy

Calixtre et al (2015) stated that there is a lack of knowledge about the effectiveness of manual therapy (MT) on subjects with TMD.  These investigators synthetized evidence regarding the isolated effect of MT in improving maximum mouth opening (MMO) and pain in subjects with signs and symptoms of TMD.  MEDLINE, Cochrane, Web of Science, SciELO and EMBASE electronic databases were consulted, searching for RCTs applying MT for TMD compared to other intervention, no intervention or placebo.  Two authors independently extracted data, PEDro scale was used to assess risk of bias, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) was applied to synthetize overall quality of the body of evidence.  Treatment effect size was calculated for pain, MMO and PPT.  A total of 8 trials were included, 7 of high methodological quality.  Myofascial release and massage techniques applied on the masticatory muscles are more effective than control (low-to-moderate evidence) but as effective as toxin botulinum injections (moderate evidence).  Upper cervical spine thrust manipulation or mobilization techniques are more effective than control (low-to-high evidence), while thoracic manipulations are not.  There is moderate-to-high evidence that MT techniques protocols are effective.  The methodological heterogeneity across trials protocols frequently contributed to decreased quality of evidence.  The authors concluded that there is widely varying evidence that MT improves pain, MMO and PPT in subjects with TMD signs and symptoms, depending on the technique.  They stated that further studies should consider using standardized evaluations and better study designs to strengthen clinical relevance.

Armijo-Olivo and colleagues (2016) summarized evidence from and evaluated the methodological quality of RCTs that examined the effectiveness of MT and therapeutic exercise interventions when compared with other active interventions or standard care for treatment of TMD.  Electronic data searches were performed including 6 databases in addition to manual search; RCTs involving adults with TMD, comparing any type of MT intervention (e.g., mobilization, manipulation) or exercise therapy compared to a placebo intervention, controlled comparison intervention, or standard care were included.  The main outcomes of this systematic review were pain, range of motion (ROM) and oral function.  A total of 48 studies met the inclusion criteria and were analyzed.  Data were extracted in duplicate on specific study characteristics.  The overall evidence for this systematic review was considered low.  The trials included in this review had unclear or high risk of bias.  Thus, the evidence was generally down-graded based on risk of bias assessments.  Most of the effect sizes were low-to-moderate with no clear indication of superiority of exercises versus other conservative treatments to treat TMD.  However, MT alone or in combination with exercises at the jaw or cervical level showed promising effects.  The authors concluded that no high quality evidence was found, indicating that there is great uncertainty about the effectiveness of exercise and manual therapy for TMD.

Asquini et al (2022) noted that within physical therapy, MT is known to be effective for managing TMDs; however, MT is a broad term including different approaches used on different body regions.  In a systematic review, these investigators examined the effectiveness of MT used specifically to the cranio-mandibular structures (Cranio-Mandibular Manual Therapy [CMMT]) on pain and maximum mouth opening in patients with TMD.  This systematic review was developed based on a pre-determined published protocol that was prospectively registered with PROSPERO.  These researchers carried out a search of Medline, Embase, CINAHL, ZETOC, Web of Science, SCOPUS, PEDro, PubMed, Cochrane Library and Best Evidence, EBM reviews-Cochrane Central Register of Controlled Trials, Index to Chiropractic Literature ChiroAccess and Google Scholar databases from inception until October 2020.  RCTs comparing the effect of CMMT on pain and MMO versus other types of treatment in TMDs were included.  Two reviewers independently screened articles for inclusion, extracted data, evaluated risk of bias with the revised Cochrane risk of bias tool for randomized trials and examined the overall quality of evidence with the GRADE.  A total of 2,720 records were screened, of which only 6 (293 subjects) met the inclusion criteria.  All studies showed some concerns in risk of bias, except for 1 , which exhibited high risk of bias.  The overall quality of evidence was very low for all outcomes because of high heterogeneity and small sample sizes.  All studies reported a significant improvement in pain and maximum mouth opening for CMMT from baseline in the mid-term, but only 2 showed superiority compared to other interventions.  Given the high heterogeneity and small sample sizes of the included studies, a quantitative synthesis was not carried out.  The authors concluded that very low quality of evidence supports CMMT for patients with TMD for successfully reducing pain and improving MMO in the mid-term.  Whether CMMT is superior to other interventions remains unclear.  Clinicians planning treatment of patients with TMD may consider CMMT, in addition to other treatment modalities, as one effective, low-cost, conservative option to manage pain and improve MMO in the mid-term.  Moreover, these investigators stated that there is the need for future high-quality research examining different MT techniques used on different body regions and different populations (e.g., chronic versus acute TMD) to determine what is most effective for pain and MMO in patients with TMDs.

Permanent Mandibular Repositioning

Greene and Obrez (2015) reviewed the rationale and history of mandibular repositioning procedures in relation to TMDs as these procedures have evolved over time.  A large body of clinical research evidence showed that most TMDs can and should be managed with conservative treatment protocols that do not include any mandibular repositioning procedures.  Although this provided a strong clinical argument for avoiding such procedures, very few reports have discussed the biologic reasons for either accepting or rejecting them.  This scientific information could provide a basis for determining whether mandibular repositioning procedures can be defended as being medically necessary.  This position paper introduced the biologic concept of homeostasis as it applies to this topic.  The continuing adaptability of teeth, muscles, and temporomandibular joints throughout life is described in terms of homeostasis, which leads to the conclusion that each person's current temporomandibular joint position is biologically "correct".  Therefore, that position does not need to be changed as part of a TMD treatment protocol.  This means that irreversible TMD treatment procedures, such as equilibration, orthodontics, full-mouth reconstruction, and orthognathic surgery, cannot be defended as being medically necessary.

Phototherapy

Herpich et al (2014) stated that according to the International Association for the Study of Pain (IASP), the term TMD regards a subgroup of orofacial pain, the symptoms of which include pain or discomfort in the temporomandibular joint, ears, masticatory muscles and neck on one or both sides, as well as joint sounds, limited mandibular movements or mandibular deviation and difficulties chewing.  Phototherapy, such as low-level laser therapy (LLLT) and light-emitting diode (LED) therapy, is one of the resources used to treatment muscle pain.  Thus, there is a need to investigate therapeutic resources that combine different wavelengths as well as different light sources (LLLT and LED) in the same apparatus.  The aim of the proposed study is to evaluate the effects of 4 different doses of phototherapy on pain, activity of the masticatory muscles (masseter and bilateral anterior temporal) and joint mobility in individuals with TMD.  A further aim is to determine the cumulative effect 24 and 48 hours after a single session.  A placebo-controlled, double-blind, randomized, clinical trial will be carried out involving 72 women between 18 and 40 years of age with a diagnosis of myogenous TMD.  The participants will then be randomly allocated to 4 groups totaling 18 individuals per group; 3 groups will be submitted to a single session of phototherapy with different light sources, and 1 group will receive placebo therapy: Group A (2.62 Joules); Group B (5.24 Joules); Group C (7.86 Joules); and Group D (0 Joules).  The following assessment tools will be administered on 4 separate occasions (baseline and immediately after, 24 hours after and 48 hours after phototherapy).  Pain intensity will be assessed using the VAS for pain, while pain thresholds will be determined using algometer, and EMG analysis on the masseter and anterior temporal muscles.  The study will contribute to the practice of the evidence-based use of phototherapy in individuals with a myogenous TMD.  Data will be published after the study is completed.  This study is registered with the Brazilian Registry of Clinical Trials, NCT02018770, date of registration: December 7, 2013.

Stem Cell Therapy

Zhang et al (2015) noted that in the past decade, progress made in the development of stem cell-based therapies and tissue engineering have provided alternative methods to attenuate the disease symptoms and even replace the diseased tissue in the treatment of TMJ disorders.  Resident mesenchymal stem cells (MSCs) have been isolated from the synovia of TMJ, suggesting an important role in the repair and regeneration of TMJ.  The seminal discovery of pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have provided promising cell sources for drug discovery, transplantation as well as for tissue engineering of TMJ condylar cartilage and disc.  The authors discussed the most recent advances in development of stem cell-based treatments for TMJ disorders through innovative approaches of cell-based therapeutics, tissue engineering and drug discovery.  The effectiveness of stem cell therapy for the treatment of TMD has yet to be determined.

Transcranial Direct Current Stimulation

Oliveira et al (2015) evaluated the effect of adding transcranial direct current stimulation (tDCS) to exercises for chronic pain, dysfunction and quality of life in subjects with TMD.  Participants were selected based on the Research Diagnostic Criteria (RDC)/TMD criteria and assessed for pain intensity, PPT over temporomandibular joint and cervical muscles and quality of life.  After initial assessment, all individuals underwent a 4-week protocol of exercises and MT, together with active or sham primary motor cortex tDCS.  Stimulation was delivered through sponge electrodes, with 2 mA amplitude, for 20 mins daily, over the first 5 days of the trial.  A total of 32 subjects (mean age of 24.7 ± 6.8 years) participated in the evaluations and treatment protocol.  Mean pain intensity pre-treatment was 5.5 ± 1.4 for active tDCS group, and 6.3 ± 1.2 for sham tDCS.  Both groups showed a decrease in pain intensity scores during the trial period (time factor - F4.5, 137.5 = 28.7, p < 0·001; group factor - F1.0, 30.0 = 7.7, p < 0.05).  However, there were no differences between the groups regarding change in pain intensity (time*group interaction - F4.5, 137.5 = 1.5, p = 0.137).  This result remained the same after 5 months (t-test t = 0.29, p > 0.05).  Pressure pain thresholds decrease and improvement in quality of life were also noticeable in both groups, but again without significant differences between them.  Absolute benefit increase was 37.5 % (CI 95 %: -15.9 % to 90.9 %), and number needed to treat was 2.66.  The authors concluded that the findings of this study suggested that there is no additional benefit in adding tDCS to exercises for the treatment of chronic TMD in young adults.

Brandao Filho et al (2015) examine if cathodal tDCS over the dorsolateral prefrontal cortex has an analgesic effect on chronic TMD pain.  The investigators will run a randomized, controlled, cross-over, double-blind study with 15 chronic muscular TMD subjects.  Each subject will undergo active (1 mA and 2 mA) and sham tDCS.  Inclusion criteria will be determined by the RDC for TMD questionnaire, with subjects who have a pain VAS score of greater than 4/10 and whose pain has been present for the previous 6 months, and with a State-Trait Anxiety Inventory score of more than 42.  The influence of tDCS will be assessed through a VAS, quantitative sensory testing, quantitative electroencephalogram, and the State-Trait Anxiety Inventory score.  Some studies have demonstrated a strong association between anxiety/depression and chronic pain, where one may be the cause of the other.  This is especially true in chronic TMD, and breaking this cycle may have an effect over the symptoms and associated dysfunction.  The authors believe that by inhibiting activity of the dorsolateral prefrontal cortex though cathodal tDCS, there may be a change in both anxiety/depression and pain level.  They state that tDCS may emerge as a new tool to be considered for managing these patients.  These investigators envision that the information obtained from this study will provide a better understanding of the management of chronic TMD.  This trial was registered at clinicaltrials.gov on May 24, 2014 (Identifier: NCT02152267).

Somatosensory Testing

In a cross-over, double-blinded, placebo-controlled manner, Ayesh and associates(2008) studied the effect of intra-articular ketamine on TMJ pain and somatosensory function.  Spontaneous pain and pain on jaw function was scored by patients on 0 to 10 cm VAS for up to 24 hours.  Quantitative sensory tests: tactile, pin-prick, PPT and pressure pain tolerance were used for assessment of somatosensory function at baseline and up to 15 mins after injections.  There were no significant effects of intra-articular ketamine over time on spontaneous VAS pain measures (ANOVA: p = 0.532), pain on jaw opening (ANOVA: p = 0.384), or any of the somatosensory measures (ANOVA: p > 0.188).  The poor effect of ketamine could be due to involvement of non-NMDA receptors in the pain mechanism and/or ongoing pain and central sensitization independent of peripheral nociceptive input.  The authors concluded that there appears to be no rationale to use intra-articular ketamine injections in TMJ arthralgia patients, and peripheral NMDA receptors may play a minor role in the pathophysiology of this disorder.

Kothari and colleagues (2015) noted that the pathophysiology and underlying pain mechanisms of TMD are poorly understood.  These researchers evaluated somatosensory function at the TMJs (TMJs) and examined if conditioned pain modulation (CPM) differs between TMD pain patients (n = 34) and healthy controls (n = 34).  Quantitative sensory testing was used to assess the somatosensory function. Z-scores were calculated for patients based on reference data.  Conditioned pain modulation was tested by comparing pressure pain thresholds (PPTs) before, during, and after the application of painful and non-painful cold stimuli.  Pressure pain thresholds were measured at the most painful TMJ and thenar muscle (control).  Data were analyzed with analyses of variance.  Most (85.3 %) of the patients exhibited at least 1 or more somatosensory abnormalities at the most painful TMJ with somatosensory gain with regard to PPT and punctate mechanical pain stimuli, and somatosensory loss with regard to mechanical detection and vibration detection stimuli as the most frequent abnormalities.  There was a significant CPM effect (increased PPT) at both test sites during painful cold application in healthy controls and patients (p < 0.001).  There was no significant difference in the relative CPM effect during painful cold application between groups (p = 0.227).  The authors concluded that somatosensory abnormalities were commonly detected in TMD pain patients and CPM effects were similar in TMD pain patients and healthy controls.

Genetic Testing

Sangani and associates (2015) stated that the TMJ is a bilateral synovial joint between the mandible and the temporal bone of the skull and TMDs are a set of complicated and poorly understood clinical conditions, in which TMDs are associated with a number of symptoms including pain and limited jaw movement.  The increasing scientific evidence suggests that genetic factors play a significant role in the pathology of TMDs.  However, the underlying mechanism of TMDs remains largely unknown.  These researchers determined the associated genes to TMDs in humans and animals.  The literature search was conducted through databases including Medline (Ovid), Embase (Ovid), and PubMed (NLM) by using scientific terms for TMDs and genetics in March 2015.  Additional studies were identified by searching bibliographies of highly relevant articles and Scopus (Elsevier).  Systematic analyses identified 31 articles through literature searches, and a total of 112 genes were identified to be significantly and specifically associated with TMDs.  The authors concluded that this systematic review provided a list of accurate genes associated with TMDs and suggested a genetic contribution to the pathology of TMDs.

Hattori and colleagues (2015) noted that synovial fibroblasts contribute to the inflammatory TMJ under pathogenic stimuli.  Synovial fibroblasts and T cells participate in the perpetuation of joint inflammation in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other.  IL-17 is an inflammatory cytokine produced primarily by Th17 cells that plays critical role in the pathogenesis of numerous autoimmune and inflammatory diseases.  These researchers investigated the roles of IL-17A in TMD using genome-wide analysis of synovial fibroblasts isolated from patients with TMD.  IL-17 receptors were expressed in synovial fibroblasts as assessed using real-time polymerase chain reaction (PCR).  Microarray analysis indicated that IL-17A treatment of synovial fibroblasts up-regulated the expression of IL-6 and chemokines.  Real-time PCR analysis showed that the gene expression of IL-6, CXCL1, IL-8, and CCL20 was significantly higher in IL-17A-treated synovial fibroblasts compared to non-treated controls.  IL-6 protein production was increased by IL-17A in a time- and a dose-dependent manner.  Additionally, IL-17A simulated IL-6 protein production in synovial fibroblasts samples isolated from 3 patients.  Furthermore, signal inhibitor experiments indicated that IL-17-mediated induction of IL-6 was transduced via activation of NFκB and phosphatidylinositol 3-kinase/Akt.  The authors concluded these results suggested that IL-17A is associated with the inflammatory progression of TMD.

Nicot and co-workers (2016) stated that dento-facial deformities are dysmorpho-functional disorders involving the TMJ.  Many investigators have reported a TMJ improvement in dysfunctional subjects with malocclusion after orthodontic or combined orthodontic and surgical treatment particularly for the relief of pain.  In particular, few studies have highlighted the demographic and clinical predictors of response to surgical treatment.  To-date, no genetic factor has yet been identified as a predictor of response to surgical treatment.  These researchers identified single-nucleotide polymorphisms (SNPs) associated with post-operative TMD or with TMJ symptoms after orthognathic surgery.  They found the AA genotype of SNP rs1643821 (ESR1 gene) as a risk factor for dysfunctional worsening after orthognathic surgery.  In addition, they have identified TT genotype of SNP rs858339 (ENPP1 gene) as a protective factor against TMD in a population of patients with dento-facial deformities.  Conversely, the heterozygous genotype AT was identified as a risk factor of TMD with respect to the rest of the population.  All these elements are particularly important to bring new screening strategies and tailor future treatment.  The authors concluded that the findings of this study helped to identify sub-populations at high risk of developing post-operative temporomandibular disorders after orthognathic surgery procedures.  Moreover, they stated that many other genes of interest could be potential factors influencing the dysfunctional response to orthognathic surgery, particularly genes of the Opera cohort.

Yilmaz and colleagues (2016) noted that TMJ internal derangement (TMJ ID) is a multi-factorial complex disease characterized by articular disc degeneration.  Matrilin-3 is a cartilage and bone-specific adaptor protein, and amino-acid substitutions in the protein are associated with skeletal diseases and joint disorders.  These investigators examined the variants of Matrilin-3 gene (MATN3) in a TMJ ID case-control group and investigated the risk association of the detected variants with TMJ ID.  A case control study was conducted consisting of 57 unrelated TMJ ID patients (32.7 ± 8.2) and 96 unrelated healthy controls (26.63 ± 3.05) without TMJ ID to look for associations with variants of the MATN3 gene.  DNA from individual subjects was extracted and each of the 8 exons was amplified by PCR and analyzed by single-strand conformation polymorphism (SSCP) analysis.  SSCP variants were subjected to DNA sequence analysis, which yielded band pattern variations in exon 2 of the gene.  These researchers further analyzed exon 2 by DNA sequencing to determine the sequence of these variants.  They identified SSCP band patterns variants in exon 2 of the MATN3 gene, which upon sequencing revealed a single C to T transition mutation (rs28598872) c.447 C>T (g.11608 C>T).  This polymorphism is predicted to result in a synonymous mutation (pAla149 = ).  The TT and CT genotypes were more prevalent than the CC genotype in TMJ ID patients compared to the control group with a risk factor of 2.12 (CI: 0.88 to 5.08) and 2.0 (CI: 0.726 to 5.508).  In addition, TMJ ID patients were divided into 2 groups as anterior disc displacement with reduction (ADDWR) and anterior disc displacement without reduction (ADDWOR) and compared with the controls.  The TT and CT genotypes were more prevalent than the CC genotype in ADDWR patients compared to the control group with a risk factor of 3.85 (CI: 0.927 to 16.048) and 3.75 (1.02 to 13.786), respectively.  These investigators found that, among ADDWR patients, the T allele is a risk factor both in homozygous and heterozygous carriers (p < 0.052, p < 0.036).  The authors concluded that the findings of this study indicated a potential role for the MATN3 rs28598872 polymorphism in the pathogenesis of TMJ ID.

Melis and Di Giosia (2016) performed a review of the literature of published articles assessing the role of genetic factors in the etiology of TMDs.  A PubMed search was carried out by looking for all controlled clinical trials related to the topic and limiting the search to English language and humans.  The references from the studies included and those from review articles were also examined for further relevant papers.  A total of 1,999 articles were first identified, 24 of which were considered relevant to the topic; 2 other papers were found while searching the references.  While TMD signs and symptoms' co-occurrence was not found in subjects within the same family, many gene polymorphisms were shown to be associated with a higher or lower risk of TMD.  Such genes were mainly related to serotonin activity and metabolism, T-cell receptor pathway, catecholamine activity and metabolism, estrogen activity, folate metabolism, glutathione activity, ANKH gene, major histocompatibility complex, extracellular matrix metabolism, genes studied in the orofacial pain prospective evaluation risk and assessment (OPPERA) study, and related to cytokines activity and metabolism.  The authors concluded that this new understanding of the pathophysiology of TMD can lead to a different treatment approach by identifying the subjects at higher risk for this pathology, and possibly by creating new drugs targeted at interfering with the expression of the genes that enhance such risk.

Furthermore, an UpToDate review on “Temporomandibular disorders in adults” (Scrivani and Mehta, 2016) does not mention genetic testing as a management tool.

Measurement of Circulating Omentin-1

In a case-control study, Harmon and colleagues (2016) examined the relationship between omentin-1 levels and painful TMD.  Chronic painful TMD cases (n = 90) and TMD-free controls (n = 54) were selected from participants in the multi-site OPPERA study.  Painful TMD case status was determined by examination using established Research Diagnostic Criteria for TMD (RDC/TMD).  Levels of omentin-1 in stored blood plasma samples were measured by using an enzyme linked immune-sorbent assay (ELISA).  Binary logistic regression was used to calculate the odds ratios (ORs) and 95 % CIs for the association between omentin-1 and painful TMD.  Models were adjusted for study site, age, sex, and body mass index (BMI).  The unadjusted association between omentin-1 and chronic painful TMD was statistically non-significant (p = 0.072).  Following adjustment for covariates, odds of TMD pain decreased 36 % per standard deviation increase in circulating omentin-1 (adjusted OR = 0.64; 95 % CI: 0.43 to 0.96; p = 0.031).  The authors concluded that circulating levels of omentin-1 were significantly lower in painful TMD cases than controls, suggesting that TMD pain is mediated by inflammatory pathways.

Botulinum Toxin

In a systematic review, Chen and associates (2015) evaluated the effectiveness of botulinum toxin therapy (BTX) for TMDs.  A comprehensive search of major databases through PubMed, Embase, and Cochrane CENTRAL was conducted to locate all relevant articles published from inception to October 2014.  Eligible studies were selected based on inclusion criteria and included English language, peer-reviewed publications of RCTs comparing BTX versus any alternative intervention or placebo.  Quality assessment and data extraction were done according to the Cochrane risk of bias tool and recommendations.  The entire systematic search and selection process was done independently by 2 reviewers.  A total of 5 relevant study trials were identified, involving 117 participants; 2 trials revealed a significant between-group difference in myofascial pain reduction, another trial that compared BTX with fascial manipulation showed equal effectiveness of pain relief on TMDs, while the remaining 2 trials showed no significant difference between the BTX and placebo groups.  Because of considerable variations in study methods and evaluation of results, a meta-analysis could not be performed.  The authors concluded that based on this review, no consensus could be reached on the therapeutic benefits of BTX on TMDs; a more rigorous design of trials should be performed in future studies.

Keenan (2015) evaluated the evidence on the use of BTX for TMD pain.  The author performed a comprehensive search on major databases such as PubMed, Embase and Cochrane CENTRAL.  Reference lists of the included studies were explored along with journals likely to contain studies relevant to the topic.  The search was restricted to the English language.  The inclusion criteria included RCTs and quasi-RCTs including parallel or cross-over studies comparing BTX versus any alternative intervention or placebo.  Quality assessment and data extraction were done following the Cochrane risk of bias tool and recommendations.  All of the steps in the review, including the search and selection process, were done independently by 2 reviewers.  Disagreements were discussed with one another until consensus was reached.  A total of 5 relevant studies were included in the review, which consisted of 117 participants; 2  trials revealed a significant inter-group difference in myofascial pain reduction.  Another trial that compared BTX with fascial manipulation showed no significant difference in pain relief for TMDs, while the remaining 2 trials showed no significant difference between the BTX and placebo groups.  Meta-analysis was not performed due to the considerable variation in study methods and evaluation of the results.  All 5 studies were targeted primarily on the masseter and temporalis muscles and most of them administered injections at bilateral muscle sites.  The methods used to find the muscles to target were all based on physical examination, with 3 studies using EMG as guidance.  The dose of BTX ranged from 70 U to 300 U, the majority used being 100 to 150 U.  All studies gave a single session of BTX and re-evaluated participants at least 1 month following the injection.  The authors concluded that no consensus could be reached on the therapeutic benefit of BTX on TMDs.

Awan and colleagues (2019) examined the therapeutic efficacy of BTX in the management of temporomandibular myofascial pain.  Electronic databases PubMed, Embase, Scopus, Web of Science, and gray literature were searched for randomized clinical trials until February 2018 to answer a focused question "What is the effectiveness of botulinum toxin in the management of temporomandibular myofascial pain"?  Two independent reviewers performed the study selection according to eligibility criteria.  A total of 7 studies that met the eligibility criteria were included; 2 studies showed a significant improvement in temporomandibular myofascial pain, and 1 study showed equal efficacy of BTX in comparison with facial manipulation, while the remaining studies did not report any significant difference between BTX and control group.  Due to heterogeneity in the methodology and outcome assessment, a meta-analysis and recalculation of risk could not be performed.  The authors concluded that based on these findings, the therapeutic efficacy of BTX was unclear.  These researchers stated that RCTs with better methodological criteria need to be performed to ascertain the real effectiveness of BTX.

In a systematic review, Machado and associates (2020) examined the safety and effectiveness of BTX-A for painful temporomandibular disorders.  These investigators searched for RCTs in 10 databases, from inception to February 12, 2019 (Medline, Embase, CENTRAL, LILACS, BBO, Web of Science, Scopus, ClinicalTrials.gov, WHO and OpenGrey).  They included 12 RCTs that compared BTX-A versus inactive or active interventions.  BTX-A was slightly more effective than placebo for pain reduction at 1 month: mean difference (MD) -1.74 points (0 to 10 scale), 95 % CI: -2.94 to -0.54, 3 RCTs, 60 participants, I-square (I2) = 0 %.  However, there were no significant differences at 3 and 6 months.  BTX-A was similar to no treatment for pain reduction at 3 and 6 months.  BTX-A was more effective than conventional treatment and LLLT for pain reduction at 1, 6, and 12 months, but less effective than facial manipulation for pain reduction at 3 months.  BTX-A was not associated with a significant increase in the risk of adverse events (AEs).  The quality of the evidence was low and results were insufficient to support the use of BTX-A for painful TMJs.  The authors concluded that high quality RCTs are needed to increase confidence in effect estimates.  These researchers stated that low quality evidence limited the applicability of these findings and precluded recommendations for practice.

Injection of Plasma Rich in Growth Factors

In a randomized, prospective clinical study, Fernandez Sanroman and colleagues (2016) evaluated the effectiveness of injection of plasma rich in growth factors (PRGF) after TMJ arthroscopy in patients with Wilkes stage IV internal derangement.  A total of 92 patients were randomized to 2 experimental groups: group A (42 joints) received injections of PRGF, and group B (50 joints) received saline injections.  Pain intensity on a VAS and MMO (mm) were measured before and after surgery and compared by analysis of variance (ANOVA).  The mean age of patients was 35.8 years (range of 17 to 67 years); 86 were female.  Significant reductions in pain were noted in both groups after surgery: VAS 7.9 pre-operative and 1.4 at 24 months post-operative.  Significantly better clinical results were achieved in group A than in group B only at 6 and 12 months post-operative; no significant difference was noted at 18 or 24 months after the surgical intervention; MMO increased after surgery in both groups: 26.2 mm pre-operative and 36.8 mm at 24 months post-operative.  No significant differences in MMO were found when the 2 groups of patients were compared.  The authors concluded that the injection of PRGF did not add any significant improvement to clinical outcomes at 2 years after surgery in patients with advanced internal derangement of the TMJ.

Gutierrez et al (2022) stated that intra-articular injections of PRP or PRGF have been used as therapeutic options for patients with TMD in recent years.  In a systematic review, these investigators examined the level of the available scientific evidence in the current literature on the benefits of applying PRP or PRGF injections to patients with TMD simultaneously or after arthrocentesis or arthroscopy to reduce post-operative pain and improve TMJ function.  This systematic review was carried out according to PRISMA criteria and an electronic database search was performed in the PubMed, Scopus and Cochrane databases during May 2021.  The patients in the study group were injected with intra-articular PRP or PRGF simultaneously or after arthrocentesis or arthroscopy while the patients in the control group had arthrocentesis or arthroscopy without an intra-articular injection or received an injection of hyaluronic acid or Ringer's lactate solution.  A total of 8 randomized controlled trials (RCTs) were selected.  The PRP and PRGF intra-articular injections demonstrated significant differences in terms of pain reduction in 3 studies and improved mandibular function in 2.  The authors concluded that the treatment with PRP or PRGF intra-articular injections demonstrated slightly better clinical results but of little significance in comparison with the control group.  Evidence of their effectiveness is crucial to establish them as non-invasive treatments and as an affordable option for treating some types of TMDs.  In accordance with Evidence-based dentistry principles, this review was assigned a C recommendation.

Intra-Articular Injections of Hyaluronic Acid

In a systematic review, Manfredini and colleagues (2010) examined the clinical studies on the use of hyaluronic acid (HA) injections to treat TMJ disorders performed over the last decade.  The selected papers were assessed according to a structured reading of articles format, which provided that the study design was methodologically evaluated in relation to 4 main issues:

  1. population,
  2. intervention,
  3. comparison, and
  4. outcome. 

A total of 19 papers were selected for inclusion in the review, 12 dealt with the use of HA in TMJ disk displacements and 7 dealt with inflammatory-degenerative disorders.  Only 9 groups of researchers were involved in the studies, and less than 50 % of the studies (8/19) were randomized and controlled trials.  All studies reported a decrease in pain levels independently by the patients' disorder and by the adopted injection protocol.  Positive outcomes were maintained over the follow-up period, which ranged between 15 days and 24 months.  The superiority of HA injections was shown only against placebo saline injections, but outcomes are comparable with those achieved with corticosteroid injections or oral appliances.  The available literature seems to be inconclusive as to the effectiveness of HA injections with respect to other therapeutic modalities in treating TMJ disorders.  The authors concluded that studies with a better methodological design are needed to gain better insight into this issue and to draw clinically useful information on the most suitable protocols for each different TMJ disorder..

Goiato and colleagues (2016) examined if intra-articular (IA) injections of HA are better than other drugs used in TMJ arthrocentesis, for the improvement of TMD symptoms. Two independent reviewers performed an electronic search of the Medline and Web of Science databases for relevant studies published in English up to March 2016.  The key words used included a combination of “hyaluronic acid”, “viscosupplementation”, “intra-articular injections”, “corticosteroids”, or “nonsteroidal anti-inflammatory agents” with “temporomandibular disorder”.  Selected studies were RCTs and prospective or retrospective studies that primarily investigated the application of HA injections compared to other IA medications for the treatment of TMD.  The initial screening yielded 523 articles.  After evaluation of the titles and abstracts, 8 were selected.  Full texts of these articles were accessed and all fulfilled the inclusion criteria.  These researchers found that IA injections of HA were beneficial in improving the pain and/or functional symptoms of TMDs.  However, other drug therapies (e.g., corticosteroid and NSAID injections), can be used with satisfactory results.  The authors concluded that well-designed clinical studies are needed to identify an adequate protocol, the number of sessions needed, and the appropriate molecular weight of HA for use.

Ferreira and colleagues (2018) performed a systematic review of the viscosupplementation effectiveness with HA in the management of articular TMDs.  Electronic searches were performed in the following databases: Medline (via PubMed), Scopus, Web of Science, Cochrane Library, Embase, LILACS, BBO, SIGLE (System for Information on Grey Literature in Europe), ClinicalTrials.gov, and the Brazilian Clinical Trials Registry (ReBec).  Only randomized clinical trials that evaluated the intra-articular administration of HA or its derivatives in osteoarthritis and/or anterior displacement of the TMJ disc were included.  The primary outcomes evaluated were patients' self-report of pain and/or discomfort in the TMJ.  Each study was assessed for the risk of bias, using the Cochrane collaboration's risk of bias tool.  A total of 640 studies were obtained in the electronic search.  After the application of the eligibility criteria, manual search, and duplicate removal, 21 articles were included; 5 articles classified their volunteers with internal derangements of the TMJ, in 4 articles the treatment was directed to participants with disc displacement with reduction and the other articles evaluated HA therapy in osteoarthritis.  The protocols presented heterogeneity, varying in the form of application, associated or not with arthrocentesis, number of applications, molecular weight, dose and concentration; and 9 studies presented high risk of bias.  The authors concluded that due to the heterogeneity and methodological inconsistencies of the studies evaluated, it was not possible to establish the efficacy of HA for the treatment of articular TMDs.

Fonseca and associates (2018) noted that viscosupplementation is a minimally invasive technique that replaces synovial fluid by intra-articular injection of HA.  Although effective in some joints, there is not conclusive evidence regarding TMDs.  In a case-series study, these investigators described the efficacy of a viscosupplementation protocol in intra-articular TMDs.  A total of 10 patients with a diagnosis of disc displacement and/or osteoarthritis by Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were submitted to 4 monthly injections of low or medium molecular weight HA.  Pain, mandibular function, image analysis by CT and MRI, and quality of life (QOL) were assessed at baseline and follow-ups (1 and 6 months).  Pain, jaw ROM, mandibular function, and QOL improved at follow-up evaluations.  Osteoarthritis changes decreased, and 20 % of patients improved mandibular head excursion after treatment.  Resolution of effusion and improvement in disc morphology were observed for most patients.  The authors concluded that this viscosupplementation protocol reduced pain and symptoms associated with internal derangement of TMJ, improved QOL, and showed benefits from both low and medium molecular weight HA in alternate cycles.  Moreover, they stated that randomized clinical trials of this treatment protocol should deserve attention in future researches.

The authors stated that although this trial showed promising results regarding the described protocol of viscosupplementation for TMJ, they were aware of the limitations of this work.  These researchers believed its greater contribution may be the description of a new perspective to be tested in a well-controlled clinical trial in future research studies.  The small number of patients (n = 10) and the study design as an open-label non-controlled trial did not allow inference of viscosupplementation positive effects to all TMD patients.

Derwich et al (2021) stated that TMJ osteoarthritis (TMJ OA) is a low-inflammatory disorder with multi-factorial etiology.  In a systematic review, these researchers examined the current state of knowledge regarding the mechanisms of action and the effectiveness of HA, corticosteroids (CS) and PRP in the treatment of TMJ OA.  The PubMed database was analyzed with the keywords: "(temporomandibular joint) AND ((osteoarthritis) OR (dysfunction) OR (disorders) OR (pain)) AND ((treatment) OR (arthrocentesis) OR (arthroscopy) OR (injection)) AND ((hyaluronic acid) OR (corticosteroid) OR (platelet rich plasma))".  After screening of 363 results, 16 studies were included in this review.  Arthrocentesis alone effectively reduced pain and improved jaw function in patients diagnosed with TMJ OA.  Additional injections of HA, either low-molecular-weight (LMW) HA or high-molecular-weight (HMW) HA, or CS at the end of the arthrocentesis did not improve the final clinical outcomes; and CS presented several negative effects on the articular cartilage.  Results related to additional PRP injections were inconsistent and were questionable.  The authors concluded that further studies should be multi-center, based on a larger group of patients and should answer the question of whether other methods of TMJ OA treatment, especially those that require the usage of additional intra-articular supplements, are more beneficial for the patients than simple arthrocentesis.

Intra-Articular Injections of Rituximab

In a retrospective study, Stoll and colleagues (2015) evaluated the involvement of IA infliximab (IFX) in the management of TMJ arthritis associated with juvenile idiopathic arthritis (JIA) that is refractory to systemic treatment and IA corticosteroid therapy.  Subjects were children with JIA who received IA IFX into the TMJ.  The effectiveness of treatment on the progression of acute and chronic changes was assessed by a quantitative MRI scoring system.  Median acute and chronic scores worsened by 0.25 and 0.75, respectively.  In multi-variate analysis, worsening acute scores and passage of time predicted worsening of the chronic scores.  The authors concluded that IA IFX allowed for progression of refractory TMJ arthritis in most but not all children with JIA.

Platelet-Rich Plasma

Pihut et al (2014) evaluated the regression of temporo-mandibular pain as a result of intra-articular injections of platelet-rich plasma (PRP) to patients with TMJ dysfunction previously subjected to prosthetic treatment.  The baseline study material consisted of 10 patients, aged 28 to 53 years, previously treated due to painful TMJ dysfunction using occlusal splints.  All patients underwent a specialist functional assessment of the dysfunction using the Polish version of the RDC/TMD questionnaire axis I and II.  The injection sites were determined by the method used during arthroscopic surgical procedures.  Following aspiration, 0.5 ml of PRP was injected into each TMJ.  The comparison of the intensity of pain during all examinations suggested a beneficial effect of the procedure being performed as the mean VAS score was 6.5 at examination I, 2.8 at examination II, and 0.6 at examination III.  The authors concluded that the application of the intra-articular injections of PRP into the TMJs has a positive impact on the reduction of the intensity of pain experienced by patients treated for TMJ dysfunction.  These preliminary findings need to be validated by well-designed studies.

In a systematic review, Bousnaki and Koidis (2018) examined if intra-articular injections of PRP are beneficial for the treatment of degenerative TMDs, such as TMJ osteoarthritis (TMJ-OA) and disc displacement with osteoarthritic lesions, when compared to other treatments, such as injections of HA or saline.  These researchers carried out an electronic search of the Medline and Scopus databases using combinations of the terms "temporomandibular" and "platelet rich plasma", to identify studies reported in English and published up until May 2017.  A hand-search of relevant journals and the reference lists of selected articles was also performed.  The initial screening identified 153 records, of which only 6 fulfilled the inclusion criteria and were included in this review.  Of these studies, 3 compared PRP with HA, while 3 compared PRP with Ringer's lactate or saline; 4 of the studies found PRP injections to be superior in terms of improvements in mandibular ROM and pain intensity up to 12 months after treatment, while the remaining 2 studies found similar results for the different treatments.  The authors concluded that there is slight evidence for the potential benefits of intra-articular injections of PRP in patients with TMJ-OA.  However, they stated that a standardized protocol for PRP preparation and application needs to be established.

Salivary Stress Biomarkers

Kobayashi and colleagues (2017) noted that the etiology of TMD remains a controversial issue in clinical dentistry.  These researchers examined if salivary alpha-amylase (sAA), cortisol levels, and anxiety symptoms differ between children with and without TMD.  Initially, 316 young subjects were screened in public schools (non-referred sample); 76 subjects aged 7 to 14 years were selected and comprised the TMD and control groups with 38 subjects each matched by sex, age, and the presence/absence of sleep bruxism.  Four saliva samples were collected: upon waking, 30 mins and 1 hour after awakening (fasting), and at night (at 8 PM) on 2 alternate days to examine the diurnal profiles of cortisol and sAA.  Anxiety symptoms were screened using the Multidimensional Anxiety Scale for Children (MASC-Brazilian version).  Shapiro-Wilk test, Student's t-test/Mann-Whitney U test, and correlation tests were used for data analysis.  No significant differences were observed in the salivary cortisol area under the curve (AUCG mean ± SD = 90.22 ± 63.36 × 94.21 ± 63.13 µg/dL/min) and sAA AUCG (mean ± SD = 2,544.52 ± 2,142.00 × 2,054.03 ± 1,046.89 U/mL/min) between the TMD and control groups, respectively (p > 0.05); however, the clinical groups differed in social anxiety domain (t = 3.759; CI: 2.609 to 8.496), separation/panic (t = 2.243; CI: 0.309 to 5.217), physical symptoms (U = 433.500), and MASC total score (t = -3.527; CI: -23.062 to -6.412), with a power of the test greater than 80 % and large effect size (d = 0.80), with no significant correlation between the MASC total score, cortisol, and sAA levels.  The authors concluded that although children with TMD scored higher in anxiety symptoms, no difference was observed in the salivary stress biomarkers between children with and without TMD.

In a systematic review, Alam et al (2023) examined the association between salivary biomarkers and TMD, which is a multi-factorial condition characterized by pain and dysfunction in the TMJ and surrounding structures.  Salivary biomarkers have emerged as potential diagnostic tools due to their non-invasiveness and easy accessibility; however, available evidence on salivary biomarkers in relation to TMD is limited and inconsistent.  These investigators searched electronic databases of PubMed, Embase, Web of Science, Scopus, Cochrane Library, PsychINFO, CINAHL and Medline using specific search terms and Boolean operators.  The search was limited to studies published in English that evaluated salivary biomarkers in individuals diagnosed with TMD; 2 reviewers independently screened the studies and extracted data.  ROB-2 was used to examine the risk of bias.  A total of 11 clinical studies met the inclusion criteria and were included in the review.  The findings provided consistent evidence of a clear association between salivary biomarkers and TMD.  Various biomarkers, including cortisol, IL-1, glutamate and several others, were assessed.  Some studies reported higher levels of cortisol and IL-1 in TMD patients, indicating potential involvement in stress and inflammation.  Glutamate levels were found to be elevated, suggesting a role in pain modulation.  Other biomarkers also showed alterations in TMD patients compared to controls.  The authors concluded that the findings from the included studies suggested that salivary biomarkers may play a role in TMD pathophysiology.  These researchers noted that although a definitive conclusion can be drawn regarding the specific salivary biomarkers and their association with TMD, the results must be interpreted with caution considering the heterogeneity of the biomarkers assessed.  They stated that further investigations with larger sample sizes, standardized methodology, and rigorous study designs are needed to ascertain the role of salivary biomarkers in TMD.

Bio-Oxidative Ozone Therapy

In a double-blind, randomized clinical trial, Celakil and colleagues (2017) examined the effect of bio-oxidative ozone application at the points of greatest pain in patients with chronic masticatory muscle pain.  A total of 40 women (mean age of 31.7) were selected after the diagnosis of myofacial pain dysfunction syndrome according to the Research Diagnostic Criteria for TMD (RDC/TMD).  Patients were randomly divided into 2 groups:

  1. patients received the ozone therapy at the point of greatest pain, ozone group (OG; n = 20); and
  2. patients received the sham ozone therapy at the point of greatest pain, placebo group (PG; n = 20). 

Ozone and placebo were applied 3 times/week, for a total of 6 sessions.  Mandibular movements were examined, masticator muscles tenderness were assessed and PPT values were obtained.  Subjective pain levels were evaluated using VAS.  These assessments were performed at baseline, 1 month and 3 months.  Ozono therapy decreased pain intensity and increased PPT values significantly from baseline to 1 month and 3 months in OG compared with PG; PPTs of the temporal (OG = 24.85 ± 6.65, PG = 20.65 ± 5.43, p = 0.035) and masseter (OG = 19.03 ± 6.42, PG = 14.23 ± 2.95, p = 0.007) muscles at 3 months of control (T2) were significantly higher in the OG group.  PPT value of the lateral pole was also significantly higher at T2 in the OG group (OG = 21.25 ± 8.43, PG = 15.35 ± 4.18, P = 0.012).  Mandibular movements did not show significant differences between treatment groups except right lateral excursion values at T2 (OG = 8.90 ± 1.77, PG = 6.85 ± 2.41, p = 0.003); however, OG demonstrated significantly better results over time.  Overall improvements in VAS scores from baseline to 3 months were OG 67.7 %; PG 48.4 %.  The authors concluded that although ozone therapy can be accepted as an alternative treatment modality in the management of masticatory muscle pain, sham ozone therapy (placebo) showed significant improvements in the tested parameters.  The main drawbacks of this study were its small sample size (n = 20 for the ozone group) and short-term follow-up (3 months).  These preliminary findings need to be validated in well-designed studies.

Magnetic Neurostimulator

Florian and colleagues (2017) evaluated application of the magnetic neurostimulator (Haihua model CD-9), used within the precepts of acupuncture, in treating TMD-related pain symptoms and limited mouth opening.  Analysis and discussion of this study were based on pain intensity index and range of mouth-opening evaluation before and after each session.  A total of 9 patients diagnosed with muscle TMD, referred by the surgery sector of Center Dental Specialties (CEO - I) in Piracicaba-Sao Paulo participated in this research.  The authors concluded that considering the simplicity of the technique and good results obtained, use of this device is suggested as an additional therapeutic tool for relief of TMD symptoms.  These preliminary findings need to be validated in well-designed studies.

Roj and colleagues (2018) evaluated the effect of magnetic stimulation on EMG activity in temporal muscles and masseters in patients with painful TMD using occlusal splints.  Participants consisted of 40 edentulous patients with TMD.  They were evaluated based on Helkimo Index.  Next, EMG activity of the temporal muscle and masseter were examined using 8-channel surface EMG.  All patients received acrylic occlusal splints for 12 weeks.  The group qualified for the study included 20 randomized patients, whose therapy was additionally carried out by extremely low-frequency magnetic fields for a period of 21 days.  Follow-up examinations were conducted after 3, 6 and 12 weeks with surface EMG recording of the examined muscles.  Patients received occlusal splint corrections using the T-Scan III system.  The clinical evaluation of TMD was analyzed using Helkimo index and VAS scale before and after the treatment.  All the data were analyzed using Statistica 12.5 PL.  Patients with combination therapy had lower asymmetry of temporal muscle activity.  The authors concluded that combination therapy using magnetic stimulation reduced intensity of pain in patients with TMD and decreased values of the Helkimo indices.  This was a small (n = 20 in the combined treatment group) study; and its findings were confounded by the combined therapy of magnetic stimulation and occlusal splint.  These preliminary findings need to be validated by well-designed studies.

MIRO Therapy

MIRO therapy entails the following:

  • Transcutaneous neural stimulations (TENS) to relax your muscles, increase blood flow and remove waste products.
  • TENS to relieve pain by stimulating the release of endorphins, your body’s own natural pain killer.
  • Energex pulsed radio frequency energy to reduce pain and rapidly improve symptoms. In a recent study by Tufts University School of Dental Medicine, Energex therapy was found to be highly effective in reducing pain associated with TMJ arthralgia and improving range of motion in the joint.
  • Vectra Genisys Ultrasound to reduce joint inflammation, muscle spasms and adhesions using sound waves that gently pass through your tissue to accelerate healing and repair.
  • A clear, almost invisible temporary device worn over your lower teeth to correct improper alignment of your jaw without altering any of your actual teeth.
  • Stabilize and refine your bite with periodic adjustments to the device until your symptoms are relieved or resolved.
  • Find the exact position where your muscles and joints are most comfortable to stop the cycle of pain, pills and dysfunction.
  • Multi Radiance cold laser to promote tissue healing and repair.
  • NuCalm neuroscience technology to quickly produce deep relaxation of your muscles.

There is a lack of evidence regarding the effectiveness of MIRO therapy for the treatment of TMD/TMJ dysfunctions.

Ultrasonography for the Diagnosis of Temporomandibular Disorders

Gauer and Semidy (2015) noted that ultrasonography is a noninvasive, dynamic, low-cost technique to diagnose internal derangement of the TMJ when magnetic resonance imaging is not readily available.

Hechler and associates (2018) performed a systematic review of published articles on ultrasound (US) and MRI of the TMJ in JIA to answer the question "What is the sensitivity and specificity of US as compared to MRI in diagnosing acute and chronic joint changes in patients with JIA?"  The most recent evidence was sought in published articles via a search of the PubMed, Ovid, and Embase databases.  Article appraisal was carried out by 2 reviewers.  A total of 19 articles reporting prospective or ambispective studies comparing US to MRI in TMJ imaging were found; 6 of these articles were specific to JIA patients.  The heterogeneity of these articles made comparison difficult.  Of the acute and chronic changes assessed (disk displacement, joint effusion, bony deformity), only joint effusion was appropriately assessed by multiple authors, with US having a sensitivity of 0 to 72 % and specificity of 70 to 83 % as compared to MRI.  There was a paucity of studies specific to JIA, with many studying adult, non-rheumatic patients.  The authors concluded that this systematic review found that dynamic imaging with high-resolution US improved sensitivity and specificity compared to static, low-resolution US.  Furthermore, there is evidence to suggest that US imaging following a baseline MRI could increase US sensitivity and specificity and may have a future role in disease surveillance.

Klatkiewicz and colleagues (2018) stated that the increased prevalence of TMDs requires searching for new, easily accessible diagnostic methods.  In addition to routine clinical examination, various methods of imaging TMJs are available, such as MRI, CT scans, or scintigraphy.  These investigators stated that US imaging, due to short examination time, low cost, and non-invasiveness, should be recommended as a routine diagnostic procedure.  These investigators examined if US imaging could be used in the diagnosis of TMJDs.  Publications during the period 2006 to March 2017 from the US National Library of Medicine database were selected for analysis by entering the terms "ultrasonography", "ultrasound", "USG", "temporomandibular joint", "TMJ", "temporomandibular disorders", and "TMD".  Papers were chosen if they met the required criteria relating to the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of this diagnostic technique with regard to imaging articular disc displacement, joint effusion, and condylar abnormalities.  The search yielded 1,883 publications, of which 8 were selected that met the criteria for inclusion in the analysis.  For articular disc displacement examinations, the following results were obtained: sensitivity 75.6 %; specificity 69.1 %; accuracy 76.1 %; PPV 72.2 %; and NPV 65.6 %.  When the examinations of joint effusion and condylar abnormalities were included, the results were respectively 66.9 %; 70.8 %; 69.9 %; 75.8 %; and 62.4 %.  The authors concluded that the use of US in the diagnosis of TMDs requires standardizing the method as well as further research to confirm its effectiveness.

Intra-Articular Injection of Analgesics for the Treatment of Temporomandibular Disorders

Gopalakrishnan and associates (2018) evaluated the efficacy of intra-articular analgesics in improving outcomes after TMJ arthrocentesis.  These researchers carried out an electronic search of PubMed, Scopus, and Google scholar databases for papers in English published up to December 2017 reporting the use of intra-articular analgesics after TMJ arthrocentesis; RCTs, controlled clinical trials (CCTs), comparative studies, retrospective studies, and case series were included while case reports, technical reports, animal studies, cadaveric studies, and review papers were excluded.  Of the 6 studies included in the review, 3 were RCTs, 2 were randomized comparative studies, and 1 was a retrospective study.  Both opioids and NSAIDs have been used after TMJ arthrocentesis.  Morphine, tramadol, fentanyl, buprenorphine, tenoxicam, and COX-2 inhibitors are the drugs used to-date.  Placebo-controlled studies reported improved outcomes after TMJ arthrocentesis with morphine and fentanyl; but no such results with buprenorphine and tenoxicam.  Tramadol was found to be better than COX-2 inhibitor.  The quality of literature was not high.  The authors concluded that there is inconclusive evidence in literature on the benefits of using intra-articular analgesics after TMJ arthrocentesis.  They stated that well-designed high-quality RCTs with standard protocol studying the effects of intra-articular opioids and NSAIDS after TMJ arthrocentesis would provide stronger evidence on its use.

Minimally Invasive and Surgical Treatments for Recurrent TMJ Dislocation

Tocaciu and colleagues (2019) stated that recurrent TMJ dislocation can be challenging to treat and the current understanding regarding etiology and management of this condition is limited.  These researchers carried out a systematic review regarding the management of recurrent TMJ dislocation.  They performed a literature review using preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines to identify papers published between 2006 and 2016.  The resultant papers were analyzed.  A total of 33 papers were found relevant to the study.  Minimally invasive techniques described included autologous blood injection, which was associated with an overall success of 80 % at 12 months.  Other modalities investigated included OK-432 sclerotherapy, laser capsulorrhaphy, botulinum toxin of the lateral pterygoid muscle or modified dextrose.  These publications showed promising success rates.  Surgical techniques described included disc plication, eminoplasty and eminectomy.  These modalities had a similar success rate, although numbers were limited.  The true incidence of recurrent TMJ dislocation is unknown and etiology is limited to expert opinion.  The authors concluded that the current understanding of management for recurrent TMJ dislocation is limited to case series and case reports.  This paper compiled the current understanding of management of recurrent TMJ dislocation.  Compared to previous reviews, this paper described some novel minimally invasive techniques with promising success in the management of recurrent TMJ dislocation.

In a systematic review and meta-analysis, Nagori and associates (2019) examined the efficacy of dextrose prolotherapy in improving outcomes in patients with TMJ hypermobility as compared to placebo.  An electronic search of PubMed, Scopus, CENTRAL and Google scholar databases was performed for English language papers published up to February 2018; RCTs and controlled clinical trials (CCTs) comparing dextrose prolotherapy with placebo for TMJ hypermobility were included.  A total of 3 RCTs were included in the review.  Frequency of subluxation/dislocation was reported by 2 trials that found no difference between dextrose and placebo.  A statistical significant difference in reduction of MMO with the use of dextrose prolotherapy was seen on pooling of data (random: MD = -3.32, 95 % CI: -5.26 to -1.28;pP = 0.0008; I2  = 0 %).  A statistical significant difference in pain reduction was also seen with dextrose as compared to placebo (random: MD = -1, 95 % CI: -1.58 to -0.42; p = 0.0007; I2  = 0 %).  The authors concluded that within the limitations of the study, dextrose prolotherapy may cause significant reduction in mouth opening and pain associated with TMJ hypermobility.  Conclusions with regard to reduction of episodes of subluxation/dislocation cannot be drawn.  These researchers stated that there is a need of more high-quality RCTs with larger sample size and homogenous prolotherapy protocol to draw stronger conclusions on the effect of dextrose prolotherapy in patients with TMJ hypermobility.

Intra-Articular Corticosteroid Injection for the Treatment of Temporomandibular Joint Disorder

Kopp and Wenneberg (1981) examined the long-term effect (2 years) of occlusal treatment and intra-articular injections of a mixture of corticosteroid and local anesthetic in 2 groups of patients with pain and dysfunction in the TMJ.  A total of 15 patients were treated with injections and 18 patients with occlusal adjustment.  The TMJ was tender to palpation in all patients.  The intra-articular injections were given once-weekly for 3 weeks.  The occlusal treatment included splints, grinding on natural teeth and occlusal correction of complete dentures.  The severity of the subjective symptoms and clinical signs was estimated before and after treatment.  Both sorts of treatment reduced the subjective symptoms and the clinical signs significantly, but the reduction was significantly greater after the intra-articular injections.  The effect of the injections was less efficient in patients with radiographic signs of re-modelling of the TMJ and general joint symptoms.  The authors concluded that both intra-articular injections of corticosteroid combined with local anesthetic and occlusal treatment had a long palliative effect on TMJ pain and dysfunction.  The intra-articular treatment, however, had a greater effect on the clinical signs.

Arabshahi et al (2005) examined the effects of CT-guided injection of corticosteroid into the TMJ in children with JIA and clinical and MRI evidence of TMJ inflammation.  A total of 23 children aged 4 to 16 years with JIA and MRI evidence of TMJ inflammation received CT-guided TMJ injections of corticosteroid (triamcinolone acetonide [n = 16] or triamcinolone hexacetonide [n = 7]).  Jaw pain or dysfunction and maximal incisal opening (MIO) distance were assessed before and after injection; 14 patients had follow-up MRI studies of the TMJ 6 to 12 months after injection.  Of the 13 patients with symptoms of jaw pain prior to corticosteroid treatment, 10 (77 %) had complete resolution of pain (p < 0.05).  Prior to corticosteroid injection, MIO in all 23 patients was below age-matched normal values.  After injection, the MIO was improved by at least 0.5 cm in 10 patients (43 %) (p = 0.0017).  Patients under 6 years of age at the time of injection showed the best response, with a post-injection MIO similar to that in age-matched controls (p = 0.2267).  There was involvement of 23 TMJs in the 14 patients who had follow-up MRI studies; resolution of effusions was observed in 11 (48 %) of the TMJs.  Other than short-term facial swelling in 2 patients, there were no side effects.  The authors concluded that the majority of children with symptomatic TMJ arthritis improved after intra-articular corticosteroid injection.  Approximately 50 % the patients experienced significant improvement in MIO and TMJ effusion.  These data suggested that corticosteroid injection may be a useful procedure for the prevention and treatment of morbidities associated with TMJ arthritis in JIA.

Parra et al (2010) noted that JIA has an incidence that ranges from 1 to 22 per 100,000 children worldwide, with involvement of the TMJ in 17 to 87 % of patients.  Intra-articular corticosteroid injections are beneficial in the local treatment of JIA and of other types of arthritis.  These investigators evaluated the accuracy of an US-guided technique for visualization of needle placement within the TMJ in children.  Between January 2000 and November 2007, a total of 180 TMJ injections were performed during 116 encounters in 83 children with arthritis (71 girls, 12 boys; mean age of 12.0 years).  Access was obtained under sterile conditions using US guidance (linear 15-MHz or curvilinear 8-MHz transducers) in a coronal plane, and confirmed with CT.  To minimize radiation, a limited focused CT protocol was developed.  A bilateral injection was performed in 65 encounters (57 %); 23 children had repeat TMJ injections.  All injections were performed using US guidance; CT confirmation was used in 127/180 TMJs (70 %).  In those confirmed with CT, the needle tip was intra-articular in 91 % of cases.  Triamcinolone hexacetonide was used in 92 % of injections and triamcinolone acetonide in 8 %; 1 major complication was encountered (skin atrophy at the injection site).  The authors concluded that in their experience, TMJ injections using US guidance was a safe, effective and accurate procedure.

Foeldvari et al (2014) stated that TMJ involvement occurs in up to 80 % of patients with JIA.  Currently there are no standardized procedures regarding diagnosis and treatment of this common complication of JIA.  These researchers examined the current clinical practices in many countries regarding diagnosis and treatment of TMJ involvement in JIA.  Pediatric rheumatologists were asked to fill out a survey with 8 items regarding diagnosis and treatment of TMJ involvement.  The survey was distributed over the worldwide pediatric rheumatology electronic list-serve.  Data were collected in an Excel spread sheet and analyzed using Excel software.  A total of 87 centers responded to the survey between December 2009 and April 2010.  All responding centers were actively screening for TMJ involvement.  All centers were screening by physical examination, 85 (97 %) by history, and 2 (3 %) by imaging; 77 (88 %) centers were screening at the 1st visit and 76 (87 %) at each follow-up visit.  If imaging was requested, 77 % of the centers reported that they asked for MRI, 10 % for US, 9 % for CT and 33 % for X-ray.  The 1st-line treatment of TMJ arthritis was a non-biologic disease-modifying anti-rheumatic drugs (DMARDs) in 36 %, an NSAID in 33 %, an intra-articular corticosteroid injection in 26 %, and an anti- tumor necrosis factor (TNF) agent in 5 %.  Overall, 57 (65 %) of the centers were using intra-articular corticosteroid injections as treatment.  The authors concluded that TMJ arthritis is common among children with JIA.  This survey showed that a wide array of diagnostic and therapeutic approaches was being employed for TMJ disease in 87 international centers.  Due to this lack of agreement in how to diagnose and treat this JIA complication, these researchers believed that an expert opinion/consensus statement regarding TMJ arthritis in JIA will likely benefit patients worldwide.

Vingende et al (2018) examined if HA injection is more beneficial compared to corticosteroid in 37 TMJs.  These researchers also examined whether the efficacy of the therapy is influenced by HA molecular weight and the used protocol.  Wilkes stage, MMO and VAS were determined pre-operatively and 6 months later.  Corticosteroid application was performed once, HA was injected on a weekly bases 3 times in a row, by use of low (6 to 10 × 10(5) Dalton) or high molecular weight (24 to 36 × 10(5) Dalton) preparations.  The medical state of the patients treated with corticosteroid temporarily improved, but the symptoms returned.  Due to HA treatment, significant improvement was revealed in all parameters (p Wilkes < 0.0001; p mouth-opening = 0.0002; p VAS < 0.0001).  There was no significant relapse (T = 2.05).  The 3rd administration of HA resulted in a significant improvement of the VAS compared to the 1st and 2nd injection (T3.-1. = 20.37; T3.-2. = 9.57).  The authors concluded that HA was significantly more effective and its application for 3 times appeared to be the most effective treatment decreasing the symptoms.  The high molecular weight solution was more effective in increasing mouth opening.  In contrast to HA, corticosteroid had no prolonged effect in higher Wilkes stages.

Furthermore, an UpToDate review on “Temporomandibular disorders in adults” (Mehta, 2020) states that “Patients with jaw locking, especially when longstanding, will most often require interventions such as intraarticular corticosteroid injections or surgical interventions, such as arthrocentesis or arthroscopy.  In patients with osteoarthritis of the TMJ who have refractory symptoms, surgery may be indicated to remove the loose fragments of bone ("joint mice") and reshape the condyle.  If medical management is not effective in patients with rheumatoid arthritis, then surgical treatment may be necessary, similar to other joints in the body”.

Cryo-Analgesia for the Treatment of Temporomandibular Joint Disorder

Sidebottom (2011) noted that cryo-analgesia is a controversial adjunct to the management of chronic pain, however, no studies had examined its effect in the management of TMJ pain.  In a retrospective, 5-year study, these investigators treated 17 patients who had severe pain that had failed to respond to all forms of conventional conservative treatment and were not appropriate for simple open operation.  None had a clear indication for open operation on the joint or had too severe disease to warrant a simple procedure.  Preliminary diagnostic injections of bupivacaine to the TMJ relieved the pain.  These researchers applied the cryo-probe in the region of the auriculo-temporal nerve and TMJ capsule.  There was a small but insignificant improvement in mean mouth opening together with a significant (p = 0.000) improvement in VAS from 6.8 (range of 4 to 10) to 2.0 (range of 0 to 7); 2 patients had no change in their pain scores, and 2 had complete resolution of their pain.  The mean number of pain-free months after treatment was 7 (inter-quartile range [IQR] 3 to 15); 3 patients had long-term pain relief, and 12 temporary relief; 6 of these subsequently had successful relief after total replacement of the TMJ; 1 patient had further cryo-analgesia, 1 was referred for specialist pain management, and 1 controlled the pain with nortriptyline.  Of the 17 cases studied, 2 had temporary complications after cryo-analgesia.  The authors concluded that cryo-analgesia was a useful adjunct to the management of intractable pain in the TMJ; short-term pain relief could be attained, and long-term relief was possible in some, deferring more complex and costly treatments.

Furthermore, an UpToDate review on “Temporomandibular disorders in adults” (Mehta, 2020) does not mention cryoanalgesia as a management / therapeutic option.

Propranolol for the Treatment of Temporomandibular Disorders

Tchivileva and colleagues (2020) noted that propranolol is a non-selective beta-adrenergic receptor antagonist.  In a randomized, double-blind, placebo-controlled, parallel-group, multi-center, phase-IIb clinical trial enrolled subjects aged 18 to 65 years with temporomandibular disorder myalgia to examine the safety and effectiveness of propranolol compared with placebo in reducing facial pain.  Subjects were randomized 1:1 to either extended-release propranolol hydrochloride (60 mg, BID) or placebo.  The primary endpoint was change in facial pain index (FPI = facial pain intensity multiplied by facial pain duration, divided by 100).  Effectiveness was analyzed as a mean change in FPI from randomization to week 9 and as the proportion of subjects with greater than or equal to 30 % or greater than or equal to 50 % reductions in FPI at week 9.  Regression models tested for treatment-group differences adjusting for study site, sex, race, and FPI at randomization.  Of 299 subjects screened, 200 were randomized; 199 had at least 1 post-randomization FPI measurement and were included in intention-to-treat (ITT) analysis.  At week 9, model-adjusted reductions in mean FPI did not differ significantly between treatment groups (-1.8, 95 % CL: -6.2 to 2.6; p = 0.41). However, the proportion with a greater than or equal to 30 % reduction in FPI was significantly greater for propranolol (69.0 %) than placebo (52.6 %), and the associated number-needed-to-treat was 6.1 (p = 0.03).  Propranolol was likewise effective for a greater than or equal to 50 % reduction in FPI (number-needed-to-treat = 6.1, p = 0.03); AE rates were similar between treatment groups, except for more frequent fatigue, dizziness, and sleep disorder in the propranolol group.  The authors concluded that propranolol was not different from placebo in reducing mean FPI; but was effective in achieving greater than or equal to 30 % and greater than or equal to 50 % FPI reductions after 9 weeks of treatment among patients with temporomandibular disorders.  Moreover, these researchers stated that these findings provided sufficient evidence to justify further investigation of propranolol for TMD management.

The authors stated that this study had several drawbacks.  First, this phase-IIb clinical trial was not powered for assessments of all secondary endpoints.  To better characterize the patient population and understand treatment effects, these investigators collected many secondary endpoints encompassing several categories for exploratory analysis.  Specifically, the secondary endpoints provided background information; served as components of the composite primary endpoint; could aid in understanding the mechanisms of action of the treatment; were related to secondary hypotheses that were not major objectives of the treatment; and were intended for exploratory analyses.  Given the variety of secondary endpoints and a limited study size, no adjustment for multiplicity was performed; thus, results for these secondary endpoints should be interpreted with caution.  Second, this trial was limited to evaluation of endpoints at a follow-up of 9 weeks after randomization and a longer follow-up could be beneficial.  Third, this study did not include certain patient populations, such as patients with co-morbid hypertension, fibromyalgia, hyperthyroidism, or opioid medication use.

Artificial Intelligence Technologies for the Diagnosis of Temporomandibular Disorders

Jha et al (2022) stated that artificial intelligence (AI) algorithms have been employed to diagnose TMDs; however, studies have used different patient selection criteria, disease subtypes, input data, and outcome measures.  Thus, the performance of the AI models varies.  In a systematic review and meta-analysis, these investigators examined the available evidence on the use of AI technologies for the diagnosis of various TMD subtypes, assessed the quality of these studies, and evaluated the diagnostic accuracy of existing AI models.  The study protocol was performed based on the PRISMA protocols.  PubMed, Embase, and Web of Science databases were searched to find relevant articles from database inception to June 2022.  Studies that used AI algorithms to diagnose at least 1 subtype of TMD and those that examined the performance of AI algorithms were included.  These investigators excluded studies on orofacial pain that were not directly related to the TMD, such as studies on atypical facial pain and neuropathic pain, editorials, book chapters, and excerpts without detailed empirical data.  The risk of bias was assessed using the QUADAS-2 tool.  These researchers used Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to provide certainty of evidence.  A total of 17 articles for automated diagnosis of masticatory muscle disorders, TMJ osteoarthrosis (OA), internal derangement, and disc perforation were included; they were retrospective studies, case-control studies, cohort studies, and a pilot study; 7 studies were subjected to a meta-analysis for diagnostic accuracy.  According to the GRADE, the certainty of evidence was very low.  The performance of the AI models had accuracy and specificity ranging from 84 % to 99.9 % and 73 % to 100 %, respectively.  The pooled accuracy was 0.91 (95 % CI: 0.76 to 0.99), I2 = 97 % (95% CI 0.96-0.98, p < 0.001).  The authors concluded that various AI algorithms developed for diagnosing TMDs may provide additional clinical expertise to increase diagnostic accuracy.  However, it should be noted that a high risk of bias was present in the included studies.  Furthermore, certainty of evidence was very low.  These researchers stated that future research of higher quality is strongly recommended.

Gallium Aluminum Arsenide Laser Therapy for the Treatment of Temporomandibular Disorder with Myofascial Pain

Wu et al (2021) noted that TMD causes masticatory muscle pain and mouth opening limitations and affects patients' ability to eat, practice oral health and perform other activities of daily living (ADL).  Although the benefits of low-energy lasers in treating TMD have been reported, the results varied greatly depending on the equipment used and the energy output.  In a systemic review and meta-analysis , these investigators examined the effectiveness of a low-level gallium aluminum arsenide (GaAlAs) laser for the treatment of TMD with myofascial pain and maxillary pain.  They searched the PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases for RCTs published since database inception to April 5, 2020, that compared low-level laser treatment to sham/placebo treatment or no intervention in patients suffering from TMD with myofascial pain.  A total of 3 reviewers independently screened the literature, extracted data, and examined the quality of the included studies according to the risk-of-bias tool recommended by the Cochrane Handbook V.5.1.0 (Cochrane Collaboration, London, UK).  Then, a meta-analysis was carried out using RevMan 5.3 and Stata 15.1 software.  The data from 8 RCTs (181 patients) were analyzed.  The severity of myofascial TMD pain (measured on a VAS) at the end of treatment was significantly different between the control laser therapy and the low-level GaAlAs laser therapy (weighted mean difference [WMD] = -0.76, 95 % CI: -1.51 to 0.01, p = 0.046); at 3 to 4 weeks after treatment, there was no significant difference (WMD = 1.24, 95 % CI: -0.04 to 2.51, p = 0.057).  Furthermore, there was no significant improvement in MMO at the end of treatment (WMD = -0.03, 95 % CI: -4.13 to 4.06, p = 0.987) or at 3 to 4 weeks after treatment (WMD = 1.22, 95 % CI: -2.94 to 5.39, p = 0.565).  The authors concluded that there is insufficient evidence to draw strong conclusions regarding the effectiveness of GaAlAs laser treatment of TMD myofascial pain, especially with respect to MMO, and data from large samples are lacking.  Given the individual differences and the complexity of the disease, more evidence is needed for future clinical research and practice.

Photo-Biomodulation

Dunsdale et al (2022) noted that bite is an important function of the human stomatognathic system.  Despite this, it is commonly impaired in TMD populations.  In a systematic review, these investigators examined the effectiveness of conservative interventions on self-reported and physical measures of bite function in individuals with TMD.  This review was carried out in compliance with PRISMA guidelines.  These researchers carried out an electronic search using PubMed, CINAHL, Embase, and Cochrane Central.  Inclusion criteria were journal articles examining the effect of any non-pharmacological conservative interventions on bite function in patients diagnosed with TMD.  Risk of bias for individual studies was examined using the Cochrane risk-of-bias v2 tool, and the NIH NHLBI pre-post tool.  Data were synthesized based on outcome measures of bite function, and the quality of evidence was assessed using the GRADE approach.  A total of 11 studies were eligible for this review.  Interventions included exercise, manual therapy, needling, oral splinting, photo-biomodulation, and patient education, which were evaluated using mastication-related pain, self-reported chewing difficulty, and bite force/endurance outcome measures.  Findings suggested exercise, manual therapy, needling, oral splinting, and photo-biomodulation interventions may improve bite function in TMD, although confidence in cumulative evidence ranged from moderate to very low.  There was no evidence that patient education improved bite function.  The authors concluded that conservative interventions may be helpful I the management of bite-related impairments associated with TMD, although further research is needed to improve the quality of evidence and direct clinical guidelines.

In a systematic review with meta-analysis, Maximo et al (2022) examined the effects of low-level laser photo-biomodulation on masticatory function and mandibular movements in adults with TMD.  These investigators carried out searches in PubMed, Web of Science, Scopus, Embase, Cochrane, LILACS, ScienceDirect, and Google Scholar, using the following descriptors: "temporomandibular joint disorders", "low-level light therapy", "low-level laser therapy", "mastication", and "mandible".  Randomized clinical trials in adults with TMD, using low-level laser and assessing the mastication and mandibular movements were selected for analysis.  The titles and abstracts of all retrieved studies were read; only the studies selected in the 1st stage were read in full and assessed regarding eligibility.  After the selection, the characteristics, methodological quality, and quality of evidence of the studies included in the review were analyzed.  In the meta-analysis, the mean amplitude of mouth opening was considered as a measure of intervention effect.  A total of 10 articles were included in the review; they had quite different results especially regarding the amplitude of mouth opening, while the mastication was assessed in only 1 of them.  Most studies had a high risk of bias, demonstrating a low methodological quality.  Significantly higher results for photo-biomodulation were identified in the 6 studies included in the meta-analysis.  The authors concluded that due to the scarcity in the literature, there is insufficient evidence of the effects of low-level laser photo-biomodulation on mastication.  As for the mandibular movements, this intervention presented significant results, especially in the amplitude of mouth opening.  Moreover, these researchers stated that further clinical trials are needed, with more homogeneous, high-quality protocols, to find new clinical approaches and scientific evidence that can be replicated, especially in the field of speech-language-hearing pathology, which had few studies focused on the masticatory function.

The authors stated that this systematic review had several drawbacks.  First, the analysis of the studies revealed considerable variability.  This may be due to the characteristics of each study, which used rather diverging methodologies (sample size, type of intervention, power, energy dose, time of application, etc.).  Therefore, even though there were some positive effects regarding the effectiveness of laser on TMD, the diversity of methodological parameters interfered with the conclusions obtained in each study, whose results were different from and conflicting with one another.  Second, besides the methodological differences found between the studies, they had a low quality of evidence, with a considerable bias in most studies.  Moreover, the studies lacked some data, making it difficult to obtain information for a quantitative synthesis that would include all the results, enabling a broader analysis.

Therefore, this study verified that low-level laser (LLL)  PBM did not provide evidence of the effect of LLL on the masticatory function, although it demonstrated beneficial effects in terms of increasing the amplitude of the mandibular movements.  The LLL therapy had positive impacts on the increase of the amplitude of mouth opening, with better results than the other interventions or the absence of treatment, as demonstrated in the meta-analysis.

Farshidfar et al (2023) noted that TMDs are the most prevalent non-dental origin orofacial pain conditions affecting the TMJs and/or orofacial muscles.  Photobiomodulation therapy (PBMT) is a conservative approach to improve function and reduce symptoms in patients with TMD. In a systematic review, these investigators updated evidence regarding the effects of PBMT on pain intensity, TMJ movements, EMG activity, PPT, and TMJ sound in patients with TMDs.  They carried out a systematic literature search in Web of Science, PubMed/Medline, and Scopus databases using appropriate keywords and specific strategies from January 2000 to September 2022.  Data extraction was carried out based on the inclusion/exclusion criteria.  A total of 40 studies were included.  All included studies except 1 provided information on pain intensity; 27 studies showed a reduction in pain intensity in PBMT groups compared to control groups; 7 out of 15 studies, which reported MMO, showed a greater MMO in PBMT groups than in placebo groups.  Furthermore, the figures for passive MMO (PMMO) and active MMO (AMMO) in all the studies reporting PMMO and AMMO were higher in PBMT groups.  In 8 out of 10 studies, lateral movement (LM) was greater in PBMT groups.  Moreover, in 3 studies out of 4, protrusive movement (PM) was reported to be greater in the PBMT group; 4 out of 9 studies showed a greater PPT in the PBMT group.  Reduced TMJ sounds in the PBMT group were reported in 2 out of 5 studies.  Additionally, in most studies, no difference in EMG activity was detected between the 2 groups.  The authors concluded that this updated systematic review demonstrated the promising effects of PBMT on the alleviation of pain and improvement in MMO.  Using the infra-red diode laser with a wavelength ranging between 780 nm and 980 nm, an energy density of less than 100 J/ cm2, and an output power of 500 mW or less for at least 6 sessions of treatment appeared to be a promising option for the treatment of TMDs signs and symptoms based on the previously reported findings.  Moreover, these researchers stated that since various parameters play a crucial role in defining a specific PBMT protocol for treating TMD, the current findings open new doors for future studies to design a standard protocol in this regard.

Surface Electromyography in the Assessment of Pain-Related Temporomandibular Disorders

In a systematic review, Szyszka-Sommerfeld et al (2023) provided a comprehensive overview of available evidence on the evaluation of masticatory muscle activity (MMA) in individuals diagnosed with pain-related TMD (TMD-P), via the use of surface EMG (sEMG).  These investigators searched electronic databases (PubMed, Web of Science, Scopus, and Embase) using specific keywords including: "pain" AND ("temporomandibular disorder*" OR "temporomandibular dysfunction*") AND "surface electromyography" AND "masticatory muscle activity".  The inclusion criteria were studies assessing MMA in patients with TMD-P using sEMG.  The Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies was utilized to assess the quality of the studies that were included in the review.  The search strategy identified 450 potential articles; 14 studies met the inclusion criteria.  Global quality rating for significant part of the studies was weak.  Most studies showed greater sEMG activity of the masseter (MM) and temporal anterior (TA) muscles at rest in TMD-P subjects than in the asymptomatic controls, while the MM and TA muscles were less active in the pain-related TMD group compared to the non-TMD group during maximal voluntary clenching (MVC).  The authors concluded that there were differences in MMA in the TMD-pain population compared to a healthy control group during various tasks.  Moreover, these researchers stated that the diagnostic effectiveness of sEMG in evaluating individuals with TMD-P remains unclear.

The authors stated that this systematic review had several drawbacks.  First, most of the included studies were of weak quality according to the EPHPP tool.  Second, only 4 studies included in this review focused on the diagnostic utility in differentiating between TMD-P and asymptomatic control subjects.  Third, the use of different EMG devices and various parameters to analyze the EMG signal may affect the results among the included studies.  Fourth, clinicians should also be aware that the differences in study groups characteristics such as gender, age, TMD subgroup may affect the EMG results.  Fifth, as the reliability and validity of sEMG largely depends on biological, instrumental and technical factors, further investigations are needed to examine the quality of EMG testing and reporting procedures using a standardized framework.

Combination Therapy (Counseling, Manual Therapy, Physical Therapy, and Splint Therapy)

In a systematic review, Vieira et al (2023) examined the effects of manual therapy on pain intensity, MMO, and disability in patients with TMDs.  These investigators carried out searches in 6 databases for RCTs.  Selection of trials, data extraction, and methodological quality assessment were carried out by 2 reviewers with discrepancies resolved by a 3rd reviewer.  Estimates were presented as MDs or standardized MDs (SMDs) with 95 % CIs.  Quality of the evidence was evaluated using the GRADE approach.  A total of 20 studies met the eligibility criteria and were included.  For pain intensity, high and moderate quality evidence showed the additional effects of manual therapy at short-term (95 % CI: -2.12 to -0.82 points) and long-term (95 % CI -2.17 to -0.40 points) on the 0 to 10 points scale.  For MMO, moderate-to-high quality evidence was found in favor of manual therapy alone (95 % CI: 0.01 to 7.30 mm) and its additional effects (95 % CI: 1.58 to 3.58 mm) at short-term and long-term (95 % CI: 1.22 to 8.40 mm).  Moderate quality evidence showed an additional effect of manual therapy for disability (95 % CI: -0.87 to -0.14).  The authors concluded that they found moderate-to-high quality evidence of the positive effects of manual therapy modalities for pain intensity, MMO and disability in patients with TMDs; however, the effect sizes were small and may not be clinically important.  Moreover, these researchers stated that future high-quality RCTs with larger sample sizes are needed to examine the effects of manual therapy in the different TMD diagnosis, clarify adverse effects, and include an economic evaluation for a better decision-making process.

The authors stated that this review had several drawbacks.  First, it included RCTs with patients with any diagnosis or type/classification (myogenic, arthrogenic or mixed), as well as joint disorders.  Second, subgroup analysis for the different classification of TMD was not possible due the limited number of studies including specific types of TMD.  Third, this review was restricted to 3 clinical outcomes.  It could be valuable to examine other important clinical outcomes such as a health-related QOL (HR-QOL), PPT, and more importantly, the costs and adverse effects of the intervention.

Kelemen et al (2023) noted that TMDs are often stomatological disorders; however, their treatment is controversial.  In a systematic review and meta-analysis, these investigators compared the effectiveness of combination therapy (splint therapy along with physiotherapy, manual therapy, and counseling) with physiotherapy, manual therapy, and counseling alone.  The extent of mouth-opening and pain perception were the outcomes.  They carried out systematic searches for English publications using 4 major literature databases (Cochrane Library, Embase, PubMed, and Web of Science).  These researchers included RCTs; they calculated MDs with 95 % CI for pain perception and MMO for the 2 groups.  The Hartung-Knapp adjustment was used for cases comprising at least 5 studies.  A total of 6 studies were included in the pain perception category, and 4 were reviewed for MMO at baseline.  A total of 4 studies evaluated pain perception, and 2 assessed MMO at 1 month.  A total of 5 studies were analyzed upon comparing pain perception at baseline and 1-month follow-up.  The MD was -2.54 [95 % CI: -3.38 to -1.70] in the intervention group and -2.33 [95 % CI: -4.06 to -0.61] in the control group.  Two studies were analyzed upon comparing MMO at baseline and 1-month follow-up.  The MD in the intervention group was 3.69 [95 % CI: -0.34 to 7.72], whereas that in the control group was 3.62 [95 % CI: -3.43 to 10.67].  The authors concluded that both therapies can be used in the management of myogenic TMD.  Moreover, these researchers stated that due to the marginal differences between the baseline and 1-month values, these findings could not confirm the effectiveness of combination therapy.

Platelet-Rich Fibrin

In a systematic review and meta-analysis, Xu et al (2023) compared the effectiveness of IA injections of HA, PRP, and platelet-rich fibrin (PRF) for the treatment of patients with TMDs and summarized their mechanisms of action; RCTs published until November 13, 2021, were identified using electronic and manual searches.  Each study was examined for the risk of bias using the Cochrane risk of bias tool.  The studies found via searches were categorized by follow-up time (1, 3, or 6 months).  Evidence quality was graded according to the GRADE system.  A total of 12 RCTs were included that involved 421 patients with TMD.  The network meta-analysis showed that all treatment groups improved compared to the placebo groups in terms of pain and MMO.  For pain evaluated via the VAS, PRF exhibited better analgesic effects than PRP or HA after 1 and 3 months.  PRP appeared to be more effective than PRF was after 6 months but there were no statistically significant differences between the 2.  For MMO, the effect of PRP was superior to those of PRF and HA after 1 month; however, after 3 and 6 months, PRF provided more encouraging results in improving MMO.  The authors concluded that PRF appeared to be more effective at relieving pain and improving MMO in patients with TMD (compared with HA, and PRP); however, more studies are needed to determine the effectiveness of this treatment.

The authors stated that this network meta-analysis had several drawbacks.  First, TMD has a multi-factorial etiology.  Network meta-analysis results may be affected by the difference in diagnosis between patients in each study.  Second, according to the GRADE system, the network results contained imprecision and inconsistency.  The differences in the preparation scheme and dosage of PRP presumably generated differences in the effect of PRP, which affected some comparisons between studies.  Third, the centrifugal parameters and dose used in several studies were not reported, leading to subgroup analysis difficulties.  Fourth, a small sample size also contributed to the difference in results despite a relatively low bias risk.

Telemedicine in the Diagnosis and Management of Temporomandibular Disorders

Abdul et al (2023) stated that telemedicine (T-Med) has become increasingly popular in recent years, especially in light of the COVID-19 pandemic, which has made it difficult for some individuals to access traditional dental care.  In a systematic review, these investigators examined the use of T-Med in the diagnosis and management of TMD and its impact on general health.  The carried out an extensive search of databases using keywords such as, "telemedicine", "teledentistry", "TMJ", and "temporomandibular disorders" resulting in a total of 482 studies to be available from which eligible studies were selected.  The Risk of Bias in Observational Studies of Exposures (ROBINS-E) tool was used to evaluate methodological quality of included studies.  A total of 2 studies that fulfilled the eligibility criteria were selected; both assessed studies that indicated varying degrees of positive outcomes for patients who were intervened for TMDs using T-Med.  The authors concluded that T-Med demonstrated promising results for the diagnosis and management of TMDs, especially since the advent of the COVID-19 pandemic and thereafter.  Moreover, these researchers stated that clinical trials with larger samples and long-term outcomes are needed to validate these preliminary findings.

The authors stated that this review had several drawbacks.  First, the systematic review identified only a few relevant studies, which could restrict the generalizability and robustness of the findings by not representing the diverse patient population.  Second, telemedicine entails various platforms and technologies (e.g., video conferencing systems, remote monitoring devices or mobile applications).  The included studies employed different telemedicine modalities that could have probably affected the overall consistency and effectiveness of telemedicine in TMD diagnosis and management.  Third, T-Med lacks a physical examination, which can make it challenging to diagnose some TMD conditions accurately.  Healthcare professionals may not be able to examine the ROM of the jaw or evaluate the strength of the surrounding muscles accurately.  Therefore, T-Med may not be suitable for patients with severe or complex TMD conditions that require a more comprehensive evaluation.  Fourth, the possibility of technical difficulties.  Patients may have difficulty accessing T-Med services if they do not have access to the necessary technology or a stable internet connection.  Technical issues can also occur during a video consultation, which can result in disruptions or delays in care delivery.  Moreover, T-Med also raises issues related to patient privacy and confidentiality.  Patients need to ensure that they are using secure T-Med platforms and that their personal health information is protected.  Healthcare professionals must also adhere to strict data protection regulations to ensure that patient health information is kept secure.


References

The above policy is based on the following references:

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