What Is It?
Prolotherapy is a commonly offered alternative treatment for joint, connective tissue, and back pain. The practice consists of injecting substances into painful or dysfunctional joints and connective tissue with the intent of relieving discomfort and restoring function. There is a wide range of substances that are used with a much variation among practitioners of prolotherapy. Examples of these substances include: dextrose or other sugars, Vitamin B12, local anesthetic agents, a wide variety of herbal products, homeopathic remedies, zinc sulfate, the patient’s own blood, and hundreds of others. Often, cocktails of multiple substances are used based on the individual preferences of the practitioner.
The theoretical rationale for the practice is that the substances injected into damaged joints or connective tissue will cause inflammation and chemical or cellular activity that will lead to repair of the affected tissues. (1,2) The logic of this theory is questionable. For one thing, inflammation is a normal physiologic response to tissue injury, and is already present in damaged tissues and joints. However, the evidence is clear that excessive or prolonged inflammation interferes with healing. Arthritis, a disorder prolotherapy is supposed to treat, is by definition chronic inflammation of joints, and this inflammation is known to cause much of the pain and tissue damage associated with arthritis. In general, excessive or chronic inflammation does more harm than good, and many conventional and alternative medical therapies are intended to reduce the deleterious effects of inflammation, so deliberately causing it to induce healing seems a dubious approach.
There are theoretical arguments involving the stimulation of cells involved in healing, such as fibroblasts, or the release of growth factors and other substances that are associated with tissue repair, which might plausibly explain how prolotherapy could be beneficial. However, the in vitro research to date suggests the effects of prolotherapy agents on tissues are broad and non-specific, and such effects are as likely to be harmful as beneficial. The underlying theory is questionable but not impossible. However, without a clearly demonstrated physiological mechanism and consistent animal model and clinical research evidence, it is not enough to justify the use of this therapy or the claims often made for it.
Does It Work?
There have been a number of studies and reviews investigating the use of prolotherapy in humans, and more are ongoing. Overall, the evidence has been mixed and of generally low quality. A Cochrane Review of prolotherapy for lower back pain examined five studies involving 366 people.(3) The review concluded,
There is conflicting evidence regarding the efficacy 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. Conclusions are confounded by clinical heterogeneity amongst studies and by the presence of co-interventions.
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.
Medical studies in the literature evaluating this technology present few randomized, double-blind clinical trials that had adequate sample size and controls and that used objective outcome measures. Additionally, studies have not successfully supported the use of prolotherapy as an effective treatment for joint or ligament instability. Furthermore, several systematic reviews, a Cochrane review, and technology assessments have reported prolotherapy injections have not been proven to be as effective as or more effective than placebo injections. Additional randomized studies are needed to evaluate the efficacy of prolotherapy for joint or ligament instability. The evidence in the peer-reviewed, published scientific literature is insufficient to support the use of prolotherapy for any therapeutic indication.
Although proponents have advocated the use of prolotherapy for a range of indications, relatively few clinical uses have been studied systematically or published in the peer-reviewed literature. Results of the most recent systematic reviews are inconclusive for demonstrating the effectiveness of prolotherapy for treatment of musculoskeletal pain, and new evidence from case series would not alter these conclusions. The majority of published experimental studies have included conservative therapy with prolotherapy for relief of chronic low back pain, and to a lesser extent, osteoarthritis of the knee with varying results. Sample sizes have been insufficient on which to base national policy decisions.
These reviews are particularly useful as sources of references to studies examining prolotherapy. Reviewing the studies cited in these summaries, it is clear that the majority of positive results stem from trials without proper controls: randomization of subjects, placebo or no treatment control groups, proper blinding, etc. And because the agents used and other aspects of the treatments are inconsistent between studies, it is difficult to compare studies or to generalize from one study to a different prolotherapy treatment approach, and it is impossible to combine small studies in meta-analyses that might have greater power to determine if the treatment is truly effective.
It is often the case that smaller and less rigorously designed studies tend to have positive conclusions. As the quality and quantity of research improves, many of these results turn out not to be trustworthy. Prolotherapy in humans is currently supported by a limited quantity of low-quality research. Until stronger evidence accumulates, if it does, the practice should be viewed as an experimental therapy of unknown benefits and reserved for circumstances in which conservative management and established conventional therapies are unsuccessful.
As is also often the case, there are absolutely no rigorous, controlled clinical studies of prolotherapy in dogs and cats. The use of this approach in pets is based entirely on anecdotal evidence, which is highly unreliable, and on extrapolation from human medicine, in which the practice has little supportive evidence and is not widely accepted as a legitimate therapy. Prolotherapy might be justifiable as an experimental intervention in cases in which better studied therapies with more established physiological rationales have failed or cannot be used, but it should not be marketed with strong claims of “proven” benefits, and it should not be used in lieu of conventional treatment.
Is it Safe?
Any injection into a joint must be done with careful attention to technique to avoid introducing infection or damaging tissues, and sedation may be necessary for such treatments, so these are risks associated with but not unique to prolotherapy treatment of joints. In humans, there have been limited efforts to assess the risks of prolotherapy. One survey of practitioners of this treatment has been reported.(7)
Dagenias et al. (2006) studied the effects and adverse events related to prolotherapy for back and neck pain. The authors conducted a practitioner postal survey evaluating prolotherapy for back and neck pain in the United States and Canada. Surveys were mailed to members of the American Academy of Orthopaedic Medicine (AAOM) and the American College of Osteopathic Pain Management and Sclerotherapy (ACOPMS), both closely affiliated with prolotherapy conference, in addition to nonmembers attending the 2004 AAOM annual conference. A 50% response rate was obtained. The authors published that the side effect with the highest estimated median prevalence was temporary post-injection pain (70%), stiffness (25%), bruising (5%), and temporary numbness (1%). The most commonly reported adverse events (total of 472) were spinal headache (n=164), pneumothorax (n=123), temporary systemic reactions (n=73) and nerve damage (n=54). A total of 69 adverse events required hospitalization, and five resulted in permanent injury, secondary to nerve damage. Almost 98% of the respondents held MD or DO degrees, and 83% were board certified in related disciplines. The authors concluded that to better assess the true risk of adverse events related to prolotherapy, further well-designed clinical trials that are designed to over-come bias inherent to practitioner surveys are needed.
Overall, prolotherapy likely presents a low to moderate risk depending on the agents used and the skill and experience of the practitioner.
Prolotherapy is a purported treatment for connective tissue and joint pain and disability. It involves injecting substances which induce inflammation and other chemical and cellular reactions into affected tissues. These reactions are theorized to relieve pain and improve function. The logic of this theory is questionable, and no clear mechanism for beneficial effects from prolotherapy has been described, but it is possible that the theory could be valid.
The clinical research on prolotherapy in humans is generally of low quality and results have been mixed. There is great variation in the techniques used by different investigators, so it is difficult to compare or generalize between studies.
There is virtually no controlled research investigating prolotherapy in companion animals, and all claims made for safety and efficacy in these species are based solely on anecdotal evidence.
The use of proltherapy in pets should be viewed as experimental with unknown risks and benefits. Such treatments should be reserved for patients that have significant symptoms that have failed to respond or cannot be treated by conventional means.
1. Banks, A.R. A rationale for prolotherapy. Journal of Orthopaedic Medicine. 1991;13(3). Accessed at http://www.prolotherapy.com/articles/banks.htm July 13, 2011.
2. Robinson, NG. Prolotherapy for pain. 2007. Accessed at http://csuvets.colostate.edu/pain/Articlespdf/Prolotherapy%20for%20Pain.pdf July 13, 2011.
3. Dagenais S, Yelland MJ, Del Mar C, Schoene ML. Prolotherapy injections for chronic low-back pain. Cochrane Database of Systematic Reviews 2007, Issue 2.
4. Aetna. Clinical Policy Bulletin: Prolotherapy. Last revised May 24, 2011. Accessed at http://www.aetna.com/cpb/medical/data/200_299/0207.html July 13, 2011.
5. Cigna HealthCare Coverage Position: Prolotherapy. Last revised December 15, 2006. Accessed at http://stage.cigna.com/health/provider/medical/procedural/coverage_positions/medical/mm_0006_coveragepositioncriteria_prolotherapy.pdf July 13, 2011.
6. Adams E. Bibliography: Prolotherapy for musculoskeletal pain. Boston, MA: Veterans Administration Technology Assessment Program (VATAP); April 2008.
7. Dagenais S, Ogunseitan O, Haldeman S, Wooley JR, Newcomb RL. Side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: A survey of practitioners. Arch Phys Med Rehabil. 2006 Jul;87(7):909-13.