Prolotherapy Peer-Reviewed and Scientific Articles and Abstracts
March 17, 2011 by Dr. Marc Darrow, M.D.
Filed under Prolotherapy Medical Literature
The Medical Rationale for Prolotherapy
Millions of Prolotherapy injections are given each year. But does it work? Numerous articles have been published, (some of the more important ones are listed below) to determine just that. Is Prolotherapy a placebo? According to the published research, Prolotherapy is not a placebo, Prolotherapy stimulates healing.
Scientific and medical papers
Banks, AR. A Rationale for Prolotherapy, J Orthopedic Medicine, 1991;13:55-59.
Hackett GS, Henderson DG. Joint stabilization: An experimental, histologic study with comments on the clinical application in ligament proliferation. Amer J Surg 1955;89:968-973.
Hackett GS. Referred pain and sciatica in diagnosis of low back disabilities, JAMA 1957;63:183-185.
Hauser RA. Punishing the pain. Treating chronic pain with Prolotherapy. Rehab Manag. 1999;12(2):26-28, 30.
Klein R, Dorman T, Johnson C. Proliferant injections for low back pain: histologic changes of injected ligaments and objective measurements of lumbar spinal mobility before and after treatment. J Neurologic and Orthopedic Medicine and Surgery. 1989;10:123-126.
Klein R, Eek B, DeLong B, Mooney V. A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. J Spinal Disord. 1993;6:23-33.
Klein R, Eek B. Prolotherapy: an alternative approach to managing low back pain. J Musculoskeletal Medicine, 1997;May:45-49.
Liu Y, Tipton C, Matthes R, Bedford T, Maynard J, Walmer H. An in situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength. Connect Tissue Res. 1983;11:95-102.
Maynard J, Pedrini V, Pedrini-Mille A, Romanus B, Ohlerking F. Morphological and biochemical effects of sodium morrhuate on tendons. Journal of Orthopedic Research. 1985;3:236-248.
Ongley M, Dorman T, et al. Ligament instability of knees: a new approach to treatment. Manual Medicine 1988;3:152- 154.
Ongley M, Klein R, Dorman T, Eek B, Hubert L. A New Approach to the Treatment of Chronic Low Back Pain. Lancet 1987;2:143-146.
Reeves KD, et al. Randomized, prospective, placebo-controlled double-blind study on dextrose prolotherapy for osteoarthritic thumb and finger (dip, pip, and trapeziometacarpal) joints: evidence of clinical efficacy. The Journal of Alternative and Complementary Medicine. 2000;6(4):311-320.
Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med 2000 Mar;6(2):68-74, 77-80.
A systematic review of prolotherapy for chronic musculoskeletal pain.
Rabago D, Best TM, Beamsley M, Patterson J. A systematic review of prolotherapy for chronic musculoskeletal pain. Clin J Sport Med. 2005 Sep;15(5):376-80.
OBJECTIVE: Prolotherapy, an injection-based treatment of chronic musculoskeletal pain, has grown in popularity and has received significant recent attention. The objective of this review is to determine the effectiveness of prolotherapy for treatment of chronic musculoskeletal pain. DATA SOURCES: We searched Medline, PreMedline, Embase, CINAHL, and Allied and Complementary Medicine with search strategies using all current and historical names for prolotherapy and injectants. Reference sections of included articles were scanned, and content area specialists were consulted. STUDY SELECTION: All published studies involving human subjects and assessing prolotherapy were included. MAIN RESULTS: Data from 34 case reports and case series and 2 nonrandomized controlled trials suggest prolotherapy is efficacious for many musculoskeletal conditions. However, results from 6 randomized controlled trials (RCTs) are conflicting. Two RCTs on osteoarthritis reported decreased pain, increased range of motion, and increased patellofemoral cartilage thickness after prolotherapy. Two RCTs on low back pain reported significant improvements in pain and disability compared with control subjects, whereas 2 did not. All studies had significant methodological limitations.
CONCLUSIONS: 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.
TemporoMandibular Joints (TMJ)
Hakala RV. Prolotherapy (proliferation therapy) in the treatment of TMD.
Cranio. 2005 Oct;23(4):283-8.
Proliferation therapy, or “prolotherapy,” is also known as regenerative injection therapy (RIT). Since the 1930s, the technique has been used to stabilize injured joints and to relieve joint pain. This article reviews the history and scientific literature regarding prolotherapy and describes the application of the technique to treat injured or unstable temporomandibular joints (TMJ). Alternative medicaments and the likely mechanisms of action are discussed. A brief preliminary summary of a retrospective clinical study of the efficacy of prolotherapy is included. The study shows that prolotherapy can be an effective therapeutic modality that reduces TMJ pain and joint noise in a majority of patients who have reached a plateau with use of an intraoral appliance, physical therapy, and home care.
The use of therapeutic medications for soft-tissue injuries in sports medicine.
Paoloni JA, Orchard JW. The use of therapeutic medications for soft-tissue injuries in sports medicine. Med J Aust. 2005 Oct 3;183(7):384-8.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) to treat most muscle, ligament and tendon injuries should be reassessed. They have, at best, a mild effect on relieving symptoms and are potentially deleterious to tissue healing. Soft-tissue injury associated with definite inflammatory conditions such as bursitis or synovitis or involving nerve impingement does warrant short-term treatment with NSAIDs. Paracetamol has similar efficacy to NSAIDs in soft-tissue injury, is cheaper, and has a lower side-effect profile. It is the analgesic of choice for most soft-tissue injury. Cyclo-oxygenase-2 (COX-2) inhibitors should not be used to treat soft-tissue injuries unless impingement is a major feature and non-selective NSAIDs are contraindicated (eg, coexisting gastric disorder), and the patient is not at cardiovascular risk. Corticosteroid injections for tendon injuries may achieve a mild to moderate reduction in pain for up to 6 weeks. However, they do not promote tendon healing, so should generally be used only when healing is not a critical goal. Promising new therapeutic treatments for soft-tissue injuries include topical glyceryl trinitrate, aprotinin injections, and prolotherapy.
Intraligamentous injection of sclerosing solutions (prolotherapy) for spinal pain: a critical review of the literature.
Dagenais S, Haldeman S, Wooley JR. Intraligamentous injection of sclerosing solutions (prolotherapy) for spinal pain: a critical review of the literature. Spine J. 2005 May-Jun;5(3):310-28.
BACKGROUND CONTEXT: The injection of various solutions aimed at producing a sclerosing effect has been used to treat soft tissues injuries (eg, inguinal hernia) for more than 100 years. In the 1930s, this treatment approach was applied to injured joints in an attempt to stimulate connective tissue repair. Although several studies have been published about this method of treatment for various orthopedic and spinal indications (termed prolotherapy), its use remains controversial.
PURPOSE: To conduct a critical review of the literature on prolotherapy for spinal pain. STUDY DESIGN/SETTING: Critical review of the literature. METHODS: Computerized medical literature databases (Medline, CINAHL, Mantis, Cochrane Central Register of Controlled Trials) were searched to uncover all published information about the use of sclerosing injections in humans with spinal pain disorders. Search results were reviewed for relevance, and information was abstracted from full-text articles. RESULTS: Our search uncovered almost 200 reference materials in various media related to prolotherapy, including 31 clinical studies related to spinal pain. There were 26 observational cohorts and 5 randomized clinical trials (RCTs). Indications in these studies were low back pain (22), neck pain (3), cervical headaches (3) and dorsal or thoracic pain (3). A total of 20 sclerosing solutions were used in these studies; the most common was a mixture of dextrose 12.5%, glycerin 12.5%, phenol 1.25% and lidocaine 0.25%. Wide variations were found in treatment protocols, such as dose, number of treatments and use of adjunct therapies. Most cohort studies were only of moderate quality and varied greatly in the substances injected and the use of co-interventions. Most clinical studies reported positive results such as decreased pain or disability, although differences between treatment and control groups did not always reach statistical significance. Commonly reported adverse reactions to this treatment include temporary postinjection pain and stiffness. A handful of more serious adverse events were reported in the 1950s and 1960s with stronger or unknown solutions.
CONCLUSION: Prolotherapy describes a variety of treatment approaches rather than a specific protocol. Results from clinical studies published to date indicate that it 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.

