Prolotherapy is a treatment technique used for chronic myofascial pain, back pain, osteoarthritis, or sports injury. It involves repeated injections of dextrose solution or other irritating substances into the joint, tendon, or painful tissue in order to provoke a regenerative tissue response. Similar techniques have been used for about a century, but the first formal publication describing prolotherapy dates back to 1956, by Dr. George Hackett. He wrote:

Within the attachment of weakened ligaments and tendons to bone, the sensory nerves become overstimulated by abnormal tension to become not only the origin of specific local pain, but also definite areas of referred pain throughout the body to as far as the head, fingers and toes from specific relaxed ligaments and tendons.

Prolotherapy. A treatment to permanently strengthen the “weld” of disabled ligaments and tendons to bone by stimulating the production of new bone and fibrous tissue cells has been developed.

Initially the concept, referred to a sclerotherapy, was that the injections formed scar tissue to stabilize the joint, tendon, or ligament. The newer concept, called prolotherapy, is that the injections provoke the proliferation of tissue, allowing for limited regeneration.

The exact response to the injections is not currently known, and so explanations of mechanism remain speculative. The notion that injecting an irritant would cause a positive proliferation of tissue resulting in improved function seems implausible. This is not enough to condemn the treatment — something is physically happening and it is possible that a useful local phenomenon is occurring. It’s possible, for example, that even without tissue regeneration, there can be a decrease in local pain or inflammation.

Therefore speculative explanations as to how prolotherapy might work are insufficient to recommend the treatment, but neither does low plausibility rule out an effect. In this case clinical evidence is critical.

It has been almost 60 years since Hackett’s first edition describing prolotherapy. In that time prolotherapy has remained on the fringe, without sufficient high-quality clinical research to clearly establish its effectiveness. This is always a red flag for me. Why is the clinical research lacking over such a long period of time? Either researchers have been unable to obtain positive results with rigorous trials, or those using prolotherapy are insufficiently interested in testing whether or not the treatment actually works.

The clinical research is divided into various indications, the substances that are injected, and the specific techniques used. A thorough review of every possible application is beyond the scope of this article, so let me focus on a few of the more common uses.

Chronic low back pain

Back pain is probably not the most favorable clinical application, because it is frequently complex with multiple facets, defying any single treatment. However, if prolotherapy were providing any effect in reducing pain or improving stability it should be detectable with careful clinical trials.

A 2007 systematic review of the literature 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.

In other words, when prolotherapy can be isolated as a variable, it provided no specific benefit to back pain. When combined with other treatments known to be effective, there was a benefit. Such results are most consistent with there being no specific benefit from prolotherapy in back pain. A 2009 follow-up review concluded that there was still insufficient evidence to conclude the therapy works for back pain. There do not appear to be any rigorous studies of prolotherapy in back pain since that review.

Knee osteoarthritis

The literature for knee osteoarthritis (KOA) is a bit better than for back pain. Unfortunately, the only reviews I can find date back to 2004 or earlier. This review by Kim et al. found that the studies to date were small and of limited quality, not allowing for any firm conclusion.

A 2013 study of 90 subjects found improvement with dextrose prolotherapy over saline injections or at-home exercise. These results are positive, but still preliminary. A 2012 study of 36 subjects showed similar results. Another 2013 study, while also showing symptomatic benefit, measured cartilage volume (CV) by MRI scan and found no difference between the prolotherapy and saline groups — both continued to lose CV at the same rate over the course of the study. Other studies I found were small, prospective, or unblinded.

My summary of this research is that — preliminary clinic research comparing dextrose prolotherapy to saline injections or exercise shows a consistent symptomatic benefit, but no change in objective outcomes, like cartilage volume. This research, however, should be considered preliminary. Larger rigorous trials are needed to definitively address the issue of efficacy.

Other musculoskeletal indications

A 2005 systematic review of prolotherapy for soft tissue and musculoskeletal injuries concluded:

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 nonrandomized and randomized controlled trials. Further investigation with high-quality randomized controlled trials with noninjection control arms in studies specific to sport-related and musculoskeletal conditions is necessary to determine the efficacy of prolotherapy.

By now this language should be familiar — it is the description of preliminary clinical research.


Prolotherapy is a treatment that has been around for a long time, but still lacks definitive clinical evidence for efficacy. The plausibility of an effect is dubious, but not impossible. It does not appear to work for back pain. The best evidence exists for knee osteoarthritis, but even here the evidence is still preliminary. At best we can say that these results warrant further research.

It should be noted that the current level of evidence is completely compatible with the null hypothesis — that there is no specific effect from prolotherapy. Researcher bias, p-hacking, publication bias, mixing variables, and placebo effects can all conspire together to create the impression of a positive effect where none exists. Most of the time, encouraging preliminary research such as exists for prolotherapy is not supported by later rigorous clinical research.

Further, it seems that the practice and promotion of prolotherapy greatly exceeds what is justified by this preliminary research. I would recommend caution to anyone considering this therapy, and certainly I would not believe the hype. Proponents should conduct the type of double-blind placebo-controlled trials that can definitely determine whether or not prolotherapy has any specific effect.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the president and co-founder of the New England Skeptical Society, the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also contributes every Sunday to The Rogues Gallery, the official blog of the SGU.