1. Aetna considers prolotherapy (also known as proliferant therapy or proliferation therapy) experimental and investigational for any indications because there is inadequate evidence of its effectiveness.

2. Aetna considers Sarapin, an herbal extract that has been used as a sclerosant in prolotherapy, experimental and investigational for any indications because there is inadequate evidence of its effectiveness.

Prolotherapy refers to the injection of sclerosing solutions into joints, muscles, or ligaments. The effectiveness of prolotherapy has not been verified by scientifically controlled studies. As early as 1978, the Medical Procedures Appropriateness Program of the Council of Medical Specialty Services (CMSS), based on input from the American Academy of Orthopedic Surgeons, the American Association of Neurological Surgeons, and the American College of Physicians, concluded that prolotherapy had not been shown to be effective. Furthermore, the clinical practice guideline on "Acute Low Back Problems in Adults" by the Agency for Health Care Policy and Research does not recommend ligamentous and sclerosant injections in the treatment of patients with acute low back pain. In a recent report, Yelland et al (2004) concluded that prolotherapy is no more effective than saline injections for the treatment of chronic low back pain. Additionally, the Canadian Coordinating Office for Health Technology Assessment (2004) stated that "evidence from further controlled clinical trials of prolotherapy is clearly needed."

An assessment of prolotherapy prepared for the California Technology Assessment Forum (CTAF) concluded that prolotherapy does not meet CTAF's assessment criteria (Feldman, 2004). The assessment concluded "only one early study (Ongley et al., 1987) was able to demonstrate conclusively that prolotherapy was significantly superior to placebo for treatment of chronic low back pain. Subsequent research has not been able to replicate this finding. It is therefore not possible to conclude from the published literature that prolotherapy is superior to placebo injection for the treatment of chronic low back pain."

In a systematic review of prolotherapy for chronic musculoskeletal pain, Rabago, et al. (2005) concluded that there are limited high-quality data supporting the use of prolotherapy in the treatment of musculoskeletal pain or sport-related soft tissue injuries. Positive results compared with controls have been reported in non-randomized and randomized controlled trials. Further investigation with high-quality randomized controlled trials with non-injection control arms in studies specific to sport-related and musculoskeletal conditions is necessary to determine the effectiveness of prolotherapy. Dagenais, et al. (2005) stated that results from clinical studies published to date indicate that prolotherapy may be effective at reducing spinal pain. Great variation was found in the injection and treatment protocols used in these studies that preclude definite conclusions. Future research should focus on those solutions and protocols that are most commonly used in clinical practice and have been used in trials reporting effectiveness to help determine which patients, if any, are most likely to benefit from this treatment (Degenais, et al., 2005).

In a Cochrane review on prolotherapy injections for chronic low-back pain, Degenais et al (2007) concluded that there is conflicting evidence regarding the effectiveness of prolotherapy injections for patients with chronic low-back pain. When used alone, prolotherapy is not an effective treatment for chronic low-back pain. When combined with spinal manipulation, exercise, and other co-interventions, prolotherapy may improve chronic low-back pain and disability. These researchers noted that conclusions are confounded by clinical heterogeneity among studies and by the presence of co-interventions.

Khan and colleagues (2008) presented the results of dextrose prolotherapy undertaken for chronic non-responding coccygodynia in 37 patients (14 men and 23 women, mean age of 36 years). Patients with chronic coccygodynia not responding to conservative treatment for more than 6 months were included; 27 of them had received local steroid injections. A visual analog score (VAS) was recorded for all patients before and after injection of 8 ml of 25 % dextrose and 2 ml of 2 % lignocaine into the coccyx. In 8 patients with a VAS of more than 4 after the second injection, a third injection was given 4 weeks later. The mean VAS before prolotherapy was 8.5. It was 3.4 after the first injection and 2.5 after the second injection. Minimal or no improvement was noted in 7 patients; the remaining 30 patients had good pain relief. The authors concluded that dextrose prolotherapy is an effective treatment option in patients with chronic, recalcitrant coccygodynia and should be used before undergoing coccygectomy. They stated that randomized studies are needed to compare prolotherapy with local steroid injections or coccygectomies.

In a pilot study, Scarpone et al (2008) examined the effectiveness of prolotherapy in the treatment of lateral epicondylosis. Subjects received injections of a solution made from 1 part 5 % sodium morrhuate, 1.5 parts 50 % dextrose, 0.5 parts 4 % lidocaine, 0.5 parts 0.5 % sensorcaine and 3.5 parts normal saline. Controls received injections of 0.9 % saline. Three 0.5-ml injections were made at the supracondylar ridge, lateral epicondyle, and annular ligament at baseline and at 4 and 8 weeks. The primary outcome was resting elbow pain (0 to 10 Likert scale). Secondary outcomes were extension and grip strength. Each was performed at baseline and at 8 and 16 weeks. One-year follow-up included pain assessment and effect of pain on activities of daily living. The groups were similar at baseline. Compared to controls, prolotherapy-treated subjects reported improved pain scores (4.5 +/- 1.7, 3.6 +/- 1.2, and 3.5 +/- 1.5 versus 5.1 +/- 0.8, 3.3 +/- 0.9, and 0.5 +/- 0.4 at baseline and at 8 and 16 weeks, respectively). At 16 weeks, these differences were significant compared to baseline scores within and among groups (p < 0.001). Prolotherapy subjects also reported improved extension strength compared to controls (p < 0.01) and improved grip strength compared to baseline (p < 0.05). Clinical improvement in prolotherapy-treated subjects was maintained at 52 weeks. There were no adverse events. The authors concluded that prolotherapy with dextrose and sodium morrhuate was well-tolerated, effectively decreased elbow pain, and improved strength testing in subjects with refractory lateral epicondylosis compared to control group injections. The findings of this pilot study (with a small sample size) need to be validated by more research.

According to Martindale's Extrapharmacopoeia, Sarapin is a brand name for an extract of the pitcher plant, or Sarracenia Purpurea. Martindale's notes that "the roots and leaves of Sarracenia Purpurea have been used in the form of an aqueous distillate, administered by local injection, for neuromuscular or neuralgic pain."

Sarapin is typically administered in conjunction with prolotherapy. There is inadequate evidence of the effectiveness of Sarapin for pain. One clinical study involving 180 patients found greater pain relief in patients administered facet blocks with Sarapin than those without (Manchikanti, et al., 2000). Another study, using an animal model, found Sarapin to have no anesthetic effect (Harkins, et al., 1997). Other studies found no effect of the addition of Sarapin on neural blockade (Manchikanti, et al., 2004; Manchikanti, et al., 2006; Manchikanti, et al., 2007).