From Wikipedia, the free encyclopedia

Prolotherapy, also called proliferation therapy, is an injection-based treatment used in chronic musculoskeletal conditions.[1] It has been characterised as an alternative medicine practice.[2]

Medical uses[edit]

A 2015 review found no evidence that prolotherapy is safe or effective for Achilles tendinopathy, plantar fasciosis, and Osgood–Schlatter disease.[3] The quality of the studies was also poor.[3] Another 2015 review assigned a strength of recommendation level A for Achilles tendinopathy and knee osteoarthritis and level B for lateral epicondylosis, Osgood–Schlatter disease, and plantar fasciosis.[4] Level A recommendations are based on consistent and good-quality patient-oriented evidence while level B are based on inconsistent or limited-quality patient-oriented evidence.[4]

Low back pain[edit]

A 2007 Cochrane review of prolotherapy in adults with chronic low-back pain found unclear evidence of effect.[5] A 2009 review concluded the same for subacute low back pain.[6] A 2015 review found consistent evidence that it does not help in low back pain.[4] There was tentative evidence of benefit when used with other low back pain treatments.[5][7] Evidence of benefit remains tentative (level B) for dextrose prolotherapy in low back or sacroiliac pain.[8]


A 2009 systematic review of the efficacy in the treatment of lateral epicondylitis concluded that these therapies may benefit people with lateral epicondylitis, but the evidence was limited.[9] A 2010 review concluded moderate evidence exists to support the use of prolotherapy injections in the management of pain in lateral epicondylitis, and that prolotherapy was no more effective than eccentric exercise in the treatment of Achilles tendinopathy.[10] A 2016 review found a trend towards benefit in 2016 for lateral epicondylitis.[11] A 2017 review found tentative evidence in Achilles tendinopathy.[12]

In 2012, a systematic review studying various injection therapies found that prolotherapy and hyaluronic acid injection therapies were more effective than placebo when treating lateral epicondylitis. Of the studies evaluated, one of ten glucocorticoid trials, one of five trials for autologous blood injection or platelet-rich plasma, one trial of polidocanol, 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.[13]

Knee osteoarthritis[edit]

Tentative evidence of prolotherapy benefit was reported in a 2011 review.[5][7] One 2017 review found evidence of benefit from low-quality studies.[14] A 2017 review described the evidence as moderate for knee osteoarthritis.[15] A 2016 review found benefit but there was a moderate degree of variability between trials and risk of bias.[16] In 2019, the American College of Rheumatology recommended against prolotherapy for knee osteoarthritis.[17]


Contraindications for patients to receive prolotherapy injections may include:[18]

Relative contraindications include:[citation needed]

Side effects[edit]

Patients receiving prolotherapy injections have reported generally mild side effects, including mild pain and irritation at the injection site[20][21] (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[20] or, in rare cases, opioid medications. NSAIDs are not usually recommended due to their counter action to prolotherapy-induced inflammation, but are occasionally used in patients with pain refractory to other methods of pain control.[18] Theoretical adverse events of prolotherapy injection include lightheadedness, allergic reactions to the agent used, bruising, infection, or nerve damage. Allergic reactions to sodium morrhuate are rare.[18] 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.[7][18]


Prolotherapy involves the injection of an irritant solution into a joint space,[22] weakened ligament, or tendon insertion to relieve pain. [7] Most commonly, hyperosmolar dextrose (a sugar) is the solution used;[23] glycerine,[20] lidocaine (a commonly used local anesthetic),[24] phenol,[20] and sodium morrhuate (a derivative of cod liver oil extract) are other commonly used agents.[7][9] The injection is administered at joints, ligaments, or 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 three to six or more treatments.[18][20] Many patients receive treatment at less frequent intervals until treatments are rarely required, if at all.[25]

Terminology and mechanism[edit]

The term originated with George S. Hackett, MD, in 1956 in a publication titled "The rehabilitation of an incompetent structure by the generation of new cellular tissue". He applied the term prolotherapy from the words "proli’" (Latin), meaning offspring, and "proliferate", meaning to produce new cells in rapid succession.[26] Although the erroneous term "sclerotherapy" was utilized by some in the past to describe this treatment, it is now clear that prolotherapy does not cause scarring.[27] The mechanism of prolotherapy requires further clarification.[19][20][22][27][28][29] It is expected to involve a number of mechanisms.[1][8][30]


Some 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.[31][32][33] 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."[34]


The concept of creating irritation or injury to stimulate healing has been recorded as early as Roman times when hot needles were poked into the shoulders of injured gladiators.

In 1840, French surgeon Alfred-Armand-Louis-Marie Velpeau published a paper detailing how he had injected an iodine solution into a hernia in order to create beneficial inflammation.[35] American surgeon Joseph Pancoast later wrote that he had been performing this procedure (using either iodine or cantharides) since 1836.[35] Another early American practitioner of this method was George Heaton.[35]

After World War 1, sclerotherapy came to be a common treatment for malformations of blood vessels and the lymphatic system. This involved injecting a therapeutic liquid to shrink them.[36]

By the late 1920s, this method was used to treat hernias.[35][37] By the late 1930s, it was also used to treat ligamentous laxity.[9] In the 1950s, George S. Hackett, a general surgeon in the United States, began performing injections of irritant solutions in an effort to repair joints and hernias.[18]

In 1955, Gustav Anders Hemwall became acquainted with George Hackett at an American Medical Association meeting and started practicing the technique.[38]

Hackett coined the term "prolotherapy" for the practice, a very early appearance being in his 1956 book Ligament and Tendon Relaxation (Skeletal Disability) Treated by Prolotherapy (Fibro-Osseus Proliferation).[39]


  1. ^ a b Rabago, D; Nourani, B (2017). "Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review". Current Rheumatology Reports. 19 (6): 34. doi:10.1007/s11926-017-0659-3. PMID 28484944. S2CID 4432773.
  2. ^ Rabago, D; Slattengren, A; Zgierska, A (March 2010). "Prolotherapy in primary care practice". Primary Care. 37 (1): 65–80. doi:10.1016/j.pop.2009.09.013. PMC 2831229. PMID 20188998.
  3. ^ a b Sanderson, LM; Bryant, A (2015). "Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review". Journal of Foot and Ankle Research. 8: 57. doi:10.1186/s13047-015-0114-5. PMC 4617485. PMID 26500703.
  4. ^ a b c Covey, CJ; Sineath, MH Jr; Penta, JF; Leggit, JC (2015). "Prolotherapy: Can it help your patient?". Journal of Family Practice. 64 (12): 763–768. PMID 26844994.
  5. ^ a b c Dagenais, Simon; Yelland, Michael J; Del Mar, Chris; Schoene, Mark L; Nelemans, P (2007). "Prolotherapy injections for chronic low-back pain". Cochrane Database of Systematic Reviews. 34 (1): 49–59. doi:10.1002/14651858.CD004059.pub3. hdl:10072/26843. PMC 6986690. PMID 17443537. S2CID 21217911.
  6. ^ Staal, J Bart; De Bie, Rob A.; De Vet, Henrica C. W.; Hildebrandt, Jan; Nelemans, Patty (2009). "Injection Therapy for Subacute and Chronic Low Back Pain". Spine. 34 (1): 49–59. doi:10.1097/brs.0b013e3181909558. PMID 19127161. S2CID 32221321.
  7. ^ a b c d e f g Distel, Laura M.; Best, Thomas M. (2011). "Prolotherapy: A Clinical Review of Its Role in Treating Chronic Musculoskeletal Pain". PM&R. 3 (6): S78–81. doi:10.1016/j.pmrj.2011.04.003. PMID 21703585. S2CID 40431887.
  8. ^ a b Reeves, KD; Sit, RWS; Rabago, D (2016). "Dextrose Prolotherapy: A narrative review of basic science and clinical research, and best treatment recommendations". Physical Medicine & Rehabilitation Clinics of North America. 27 (4): 783–823. doi:10.1016/j.pmr.2016.06.001. PMID 27788902.
  9. ^ 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. PMC 2755040. PMID 19028733.
  10. ^ Coombes, Brooke K; Bisset, Leanne; Vicenzino, Bill (2010). "Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: A systematic review of randomised controlled trials" (PDF). The Lancet. 376 (9754): 1751–67. doi:10.1016/S0140-6736(10)61160-9. hdl:10072/35812. PMID 20970844. S2CID 45054853.
  11. ^ Morath, O; Kubosch, EJ; Lin, XB; Burger, C; Paul, C; Wang, ZL; Kong, FL; Welle, K; Jiang, ZC; Kabir, K (2016). "Injection therapies for lateral epicondylalgia: a systematic review and Bayesian network meta-analysis". British Journal of Sports Medicine. 50 (15): 900–908. doi:10.1136/bjsports-2014-094387. PMID 26392595. S2CID 39792649.
  12. ^ Dong, W; Goost, H; Taeymans, J; Zwingmann, J; Konstantinidis, L; Südkamp, NP; Hirschmüller, A (2017). "The effect of sclerotherapy and prolotherapy on chronic painful Achilles tendinopathy-a systematic review including meta-analysis". Scandinavian Journal of Medicine and Science in Sports. Apr 27 (1): 4–15. doi:10.1111/sms.12898. PMID 28449312. S2CID 31502425.
  13. ^ Krogh, T. P.; Bartels, E. M.; Ellingsen, T.; Stengaard-Pedersen, K.; Buchbinder, R.; Fredberg, U.; Bliddal, H.; Christensen, R. (2012). "Comparative Effectiveness of Injection Therapies in Lateral Epicondylitis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials". The American Journal of Sports Medicine. 41 (6): 1435–46. doi:10.1177/0363546512458237. PMID 22972856. S2CID 25355427.
  14. ^ Krstičević, M; Jerić, M; Došenović, S; Jeličić Kadić, A; Puljak, L (2017). "Proliferative injection therapy for osteoarthritis: a systematic review". International Orthopedics. 41 (4): 671–679. doi:10.1007/s00264-017-3422-5. PMID 28190092. S2CID 21684137.
  15. ^ Hassan, F; Trebinjac, S; Murrell, WD; Maffulli, N (2017). "The effectiveness of prolotherapy in treating knee osteoarthritis in adults: a systematic review". British Medical Bulletin. 122 (1): 91–108. doi:10.1093/bmb/ldx006. PMID 28334196.
  16. ^ Sit, RW; Chung, VCh; Reeves, KD; Rabago, N; Chan, KK; Chan, DC; Wu, X; Ho, RS; Wong, SY (2016). "Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis". Scientific Reports. 6 (May 5): 25247. Bibcode:2016NatSR...625247S. doi:10.1038/srep25247. PMC 4857084. PMID 27146849.
  17. ^ Kolasinski, Sharon L.; et al. (February 2020). "2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee". Arthritis & Rheumatology. 72 (2): 220–233. doi:10.1002/art.41142. hdl:2027.42/153546. PMC 10518852. PMID 31908163. S2CID 210041163.
  18. ^ a b c d e f 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. PMC 2831229. PMID 20188998.
  19. ^ a b c d "Prolotherapy". University of Pittsburgh Medical Center. 2012. Retrieved 16 December 2012.
  20. ^ a b c d e f Judson, Christopher H.; Wolf, Jennifer Moriatis (2013). "Lateral Epicondylitis". Orthopedic Clinics of North America. 44 (4): 615–23. doi:10.1016/j.ocl.2013.06.013. PMID 24095076.
  21. ^ Slattengren A, Rabago D, Zgierska A (Mar 2010). "Prolotherapy in Primary Care Practice". Primary Care: Clinics in Office Practice. 37 (1): 65–80. doi:10.1016/j.pop.2009.09.013. PMC 2831229. PMID 20188998.
  22. ^ a b Bauer, Brent A. (2012). "Prolotherapy: Solution to low back pain?". Mayo Clinic. Retrieved 16 December 2012.
  23. ^ Davidson, J.; Jayaraman, S. (2011). "Guided interventions in musculoskeletal ultrasound: What's the evidence?". Clinical Radiology. 66 (2): 140–52. doi:10.1016/j.crad.2010.09.006. PMID 21216330.
  24. ^ Johannes, Laura (October 19, 2010). "A Pinch of Sugar for Pain". Wall Street Journal. Retrieved 16 December 2012.
  25. ^ Banks, AR (1991). "A Rationale for Prolotherapy" (PDF). Journal of Orthopaedic Medicine. 13 (3).
  26. ^ Hackett, GS (1956). Ligament and tendon relaxation treated by prolotherapy. Springfield, IL: Charles C. Thomas.
  27. ^ a b Seidenberg, P (2008). The Sports Medicine Resource Manual. Philadelphia: Elsevier. pp. 611–9. ISBN 978-1-4160-3197-0.
  28. ^ Waldman, S (2010). Pain Management. Philadelphia: Saunders (Elsevier). pp. 1027–44. ISBN 978-1-4377-0721-2.
  29. ^ 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
  30. ^ Johnston, E; Emani, C; Kochan, A; Ghebrehawariat, K; Tyburski, J; Johnston, M; Rabago, D (2020). "Prolotherapy agent P2G is associated with upregulation of fibroblast growth factor-2 genetic expression in vitro". Journal of Experimental Orthopaedics. 7 (1): 97. doi:10.1186/s40634-020-00312-z. PMC 7719583. PMID 33280075.
  31. ^ "Clinical Policy Bulletin: Prolotherapy". Aetna, Inc. 2013. Retrieved 12 October 2013.
  32. ^ "Prolotherapy for Musculoskeletal Indications" (PDF). Medical Policy. UnitedHealthCare. 2013. Retrieved 12 October 2013.
  33. ^ "Corporate Medical Policy" (PDF). Prolotherapy. BlueCross BlueShield of North Carolina. 2013. Retrieved 12 October 2013.
  34. ^ "Decision Memo for Prolotherapy for Chronic Low Back Pain)". Centers for Medicare and Medicaid Services. Retrieved 12 October 2013.
  35. ^ a b c d De Garmo, W B (8 January 1887). "THE TREATMENT OF HERNIA BY SUBCUTANEOUS INJECTION". Medical Record. 31 (2): 35. ProQuest 88980623.
  36. ^ Ayyappan, M K; Sebastian, Jithin Jagan (2023). "Origin and Evolution of Sclerotherapy for Varicose Veins". Indian Journal of Vascular and Endovascular Surgery. 10 (3): 237–239. doi:10.4103/ijves.ijves_82_23. ISSN 0972-0820.
  37. ^ Rice, Carl O. (March 1937). "The Injection Treatment of Hernia". Annals of Surgery. 105 (3): 343–350. doi:10.1097/00000658-193703000-00004. PMC 1390347. PMID 17856937.
  38. ^ "Prolotherapy Frequently Asked Questions". Osteopathic Center for Family Medicine. Retrieved 2024-03-15.
  39. ^ Hackett, George Stuart (1958). Ligament and Tendon Relaxation (skeletal Disability) Treated by Prolotherapy (fibro-osseous Proliferation): With Special Reference to Occipito-cervical and Low Back Disability, Trigger Point Pain, Referred Pain, Headache and Sciatica. Thomas.[non-primary source needed][page needed]