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Gustav Hemwall circa 1990-1995
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Gustav Hemwall circa 1990-1995

Prolotherapy is also known as "proliferation therapy," "regenerative injection therapy,"[1] or "proliferative injection therapy". It involves injecting an otherwise non-pharmacological and non-active irritant solution into the body, generally in the region of tendons or ligaments for the purpose of strengthening weakened connective tissue and alleviating musculoskeletal pain.[2][3][4][5] The precise mechanism of action for prolotherapy is currently unclear.[6]


The concept of creating irritation or injury to stimulate healing has been recorded as early as Roman times where hot needles were poked into the shoulders of injured gladiators. Prolotherapy use began in the 1930s and was originally used in the treatment of ligamentous laxity.[7] In the 1950s Dr. George S. Hackett, a general surgeon in the United States, began performing injections of irritant solutions in an effort to repair joints and hernias.[1] This practice is what would eventually evolve into modern day prolotherapy. He was joined in this practice by Gustav Anders Hemwall in the 1950s. In 1955, Dr. Hemwall became acquainted with George Hackett at an American Medical Association meeting and started practicing prolotherapy. Dr. Hemwall was regarded as an expert in prolotherapy.

Prolotherapy in clinical practice[edit]

Prolotherapy involves the injection of an irritant solution into a joint space, weakened ligament, or tendon insertion to relieve pain.[8] Most commonly, hyperosmolar dextrose (a sugar) is the solution used;[3][9] glycerine,[6] lidocaine (a commonly used local anesthetic),[3] phenol,[6] and sodium morrhuate, a derivative of cod liver oil extract are other commonly used agents.[7][8] The injection is administered at joints or at tendons where they connect to bone.

Prolotherapy treatment sessions are generally given every two to six weeks for several months in a series ranging from 3 to 6 or more treatments.[1][6] Many patients receive treatment at less frequent intervals until treatments are rarely required, if at all.[10]

Possible indications for prolotherapy[edit]

Indications for prolotherapy may include one or more of the following:[1][3][5]


Contraindications for patients to receive prolotherapy injections may include:[1]

Relative contraindications include:

Side effects and adverse events[edit]

Patients receiving prolotherapy injections have reported generally mild side effects including: mild pain and irritation at the injection site[3][6] (often within 72 hours of the injection), numbness at the injection site, or mild bleeding. Pain from prolotherapy injections is temporary and is often treated with acetaminophen[6] or in rare cases opioid medications; NSAIDs are not usually recommended, but are occasionally used in patients with pain refractory to other methods of pain control.[1] Theoretical adverse events of prolotherapy injection include lightheadedness, allergic reactions to the agent used, bruising, infection, or nerve damage. However, allergic reactions to sodium morrhuate are rare.[1] Rare cases of back pain, neck pain, spinal cord irritation, pneumothorax, and disc injury have been reported at a rate comparable to that of other spinal injection procedures.[1][8]

Evidence-based medicine[edit]

A Cochrane review of the medical literature as of October 2006 on the efficacy of prolotherapy injections in adults with chronic low-back pain concluded:[11]

Three randomized controlled trials found that prolotherapy by itself is inadequate for chronic low-back pain, but can be beneficial when used with other low back pain treatment modalities such as spinal manipulation or corticosteroid injections.[8][11] These studies, however were based on treating non specific back pain, not the indicated tendonosis. They also were not provided in locations specific for the patient's pathology but rather at predetermined points.

Of the five studies we reviewed, three found that prolotherapy injections alone were not an effective treatment for chronic low-back pain and two found that a combination of prolotherapy injections, spinal manipulation, exercises, and other treatments can help chronic low-back pain and disability. Minor side effects such as increased back pain and stiffness were common but short-lived. Based on these five studies, the role of prolotherapy injections for chronic low-back pain is still not clear.

More recently, a 2009 systematic review of the medical literature evaluated the efficacy of injection therapies including prolotherapy in the treatment of lateral epicondylosis. The authors concluded that the current body of evidence for prolotherapy and other injection therapies suggests that these therapies may benefit patients with lateral epicondylosis, but could not make definitive conclusions due to the limited evidence available.[7] A 2010 systematic review concluded moderate evidence exists to support the use of prolotherapy injections in the management of pain in lateral epicondyalgia; the authors also concluded that prolotherapy was no more effective than eccentric exercise in the treatment of achilles tendinopathy.[12]

Again in 2012, a systematic review and meta-analysis of seventeen trials studying various injection therapies including glucocorticoids, botulinum toxin, autologous blood, platelet-rich plasma, polidocanol, glycosaminoglycan, prolotherapy, and hyaluronic acid found that prolotherapy and hyaluronic acid injection therapies were more efficacious than placebo when treating lateral epicondylosis. Of the studies evaluated, one of ten glucocorticoid trials, one of five trials for autologous blood or platelet-rich plasma, one trial of polidcanol, and one trial of prolotherapy met the criteria for low risk of bias. The authors noted that few of the reviewed trials met the criteria for low risk of bias and that there is a need for more well-controlled trials.[13]


Major medical insurance policies view prolotherapy as an investigational or experimental therapy with an inconclusive evidence base. Consequently, they currently do not provide coverage for prolotherapy procedures.[14][15][16] Medicare reviewers in 1999 determined at that time that practitioners had not provided "any scientific evidence on which to base a [different] coverage decision," and so retained Medicare's current coverage policy to not cover prolotherapy injections for chronic low back pain, but expressed willingness to reconsider if presented with results of "further studies on the benefits of prolotherapy."[17]

See also[edit]


  1. ^ a b c d e f g h Rabago, D; Slattengren, A; Zgierska, A (2010). "Prolotherapy in Primary Care Practice". Primary Care: Clinics in Office Practice 37 (1): 65–80. doi:10.1016/j.pop.2009.09.013. PMID 20188998. 
  2. ^ Brody, Jane E. (7 August 2007). "Injections to Kick-Start Tissue Repair". New York Times. Retrieved 24 July 2008. "Prolotherapy involves a series of injections designed to produce inflammation in the injured tissue." 
  3. ^ a b c d e Laura Johannes (2010). "A Pinch of Sugar for Pain". Wall Street Journal. Retrieved 16 December 2012. 
  4. ^ Brent A. Bauer (2012). "Prolotherapy: Solution to low back pain?". Mayo Clinic. Retrieved 16 December 2012. 
  5. ^ a b c d e "Prolotherapy". University of Pittsburgh Medical Center. 2012. Retrieved 16 December 2012. 
  6. ^ a b c d e f Judson, CH; Wolf, JM (October 2013). "Lateral Epicondylitis: Review of Injection Therapies". The Orthopedic Clinics of North America 44 (4): 615–623. doi:10.1016/j.ocl.2013.06.013. PMID 24095076. 
  7. ^ a b c Rabago, D; Best, TM; Zgierska, AE; Zelsig, E; Ryan, M; Crane, D (2009). "A systematic review of four injections therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood, and platelet-rich plasma". British Journal of Sports Medicine 43 (7): 471–481. doi:10.1136/bjsm.2008.052761. PMID 19028733. 
  8. ^ a b c d e f g Distel, LM; Best, TM (June 2011). "Prolotherapy: a clinical review of its role in treating chronic musculoskeletal pain". PM&R 3 (6 supplement 1): S78–S81. doi:10.1016/j.pmrj.2011.04.003. PMID 21703585. 
  9. ^ Davidson, J; Jayaraman, S (February 2011). "Guided interventions in musculoskeletal ultrasound: what's the evidence?". Clinical radiology 66 (2): 140–152. doi:10.1016/j.crad.2010.09.006. PMID 21216330. 
  10. ^ Banks, AR (1991). "A Rationale for Prolotherapy". Journal of Orthopaedic Medicine 13 (3). 
  11. ^ a b Dagenais, S; Yelland, MJ; Del Mar, C; Schoene, ML (April 2007). "Prolotherapy injections for chronic low-back pain". Cochrane Database of Systematic Reviews. CD004059. doi:10.1002/14651858.CD004059.pub3. PMID 17443537. 
  12. ^ Coombes, BK; Bisset, L; Vicenzino, B (November 2010). "Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials". Lancet 376 (9754): 1751–1767. doi:10.1016/S0140-6736(10)61160-9. PMID 20970844. 
  13. ^ Krogh, TP; Bartels, EM; Ellingsen, T; Stengaard-Pedersen, K; Buchbinder, R; Fredberg, U; Bliddal, H; Christensen, R (September 2012). "Comparative Effectiveness of Injection Therapies in Lateral Epicondylitis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials". American Journal of Sports Medicine (7). doi:10.1177/0363546512458237. PMID 22972856. 
  14. ^ "Clinical Policy Bulletin: Prolotherapy". Aetna, Inc. 2013. Retrieved 12 October 2013. 
  15. ^ "Prolotherapy for Musculoskeletal Indications". Medical Policy. UnitedHealthCare. 2013. Retrieved 12 October 2013. 
  16. ^ "Corporate Medical Policy". Prolotherapy. BlueCross BlueShield of North Carolina. 2013. Retrieved 12 October 2013. 
  17. ^ "Decision Memo for Prolotherapy for Chronic Low Back Pain)". Centers for Medicare and Medicaid Services. Retrieved 12 October 2013. 

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