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Prolotherapy is an injection-based complementary and alternative medical (CAM) therapy for chronic musculoskeletal pain. It has been used for approximately 100 years. Its modern applications, however, can be traced to the 1950s, when the prolotherapy injection protocols were formalized by George Hackett, a general surgeon in the U.S., based on his clinical experience of over 30 years. While prolotherapy techniques and injected solutions vary by condition, clinical severity, and practitioner preferences, a core principle is that a relatively small volume of an irritant or sclerosing solution is injected at sites on painful ligament and tendon insertions, and in adjacent joint space over the course of several treatment sessions. Thus, during an individual prolotherapy session, therapeutic solutions are injected at sites of painful and tender ligament and tendon insertions, and in adjacent joint spaces. Injected solutions (“proliferants”) have historically been hypothesized to cause local irritation, with subsequent inflammation and tissue healing, resulting in enlargement and strengthening of damaged ligamentous, tendon and intra-articular structures. These processes have been observed to improve joint stability, biomechanics, function and ultimately, to decrease pain.

Banks, Allen R. A rationale for prolotherapy. Journal of Orthopaedic Medicine 13, no. 3 (1991).

Cusi, Manuel, Jeni Saunders, Barbara Hungerford, Trish Wisbey-Roth, Phil Lucas, and Stephen Wilson. The use of prolotherapy in the sacroiliac joint. British Journal of sports medicine 44, no. 2 (2010): 100-104.

Dagenais, Simon, Oladele Ogunseitan, Scott Haldeman, James R. Wooley, and Robert L. Newcomb. Side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: a survey of practitioners. Archives of physical medicine and rehabilitation 87, no. 7 (2006): 909-913.

Dagenais, Simon, John Mayer, Scott Haldeman, and Joanne Borg-Stein. Evidence-informed management of chronic low back pain with prolotherapy. The Spine Journal 8, no. 1 (2008): 203-212.

Distel, Laura M., and Thomas M. Best. Prolotherapy: a clinical review of its role in treating chronic musculoskeletal pain. PM&R 3, no. 6 (2011): S78-S81.

Fullerton, Bradley D. High-resolution ultrasound and magnetic resonance imaging to document tissue repair after prolotherapy: a report of 3 cases. Archives of physical medicine and rehabilitation 89, no. 2 (2008): 377-385.

Harris, Gerald R. Effective treatment of chronic pain by the integration of neural therapy and prolotherapy. Journal of Prolotherapy 2, no. 2 (2010): 377-386.

Hooper, R. Allen, and Michele Ding. Retrospective case series on patients with chronic spinal pain treated with dextrose prolotherapy. Journal of Alternative & Complementary Medicine 10, no. 4 (2004): 670-674.

Kim, Woong Mo, Hyung Gon Lee, Cheol Won Jeong, Chang Mo Kim, and Myung Ha Yoon. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. The Journal of alternative and complementary Medicine 16, no. 12 (2010): 1285-1290.

Lyftogt, John. Subcutaneous prolotherapy treatment of refractory knee, shoulder, and lateral elbow pain. Australasian Musculoskeletal Medicine 12, no. 2 (2007): 110.

Rabago, David, Andrew Slattengren, and Aleksandra Zgierska. Prolotherapy in primary care practice. Primary Care: Clinics in Office Practice 37, no. 1 (2010): 65-80.

Rabago, David, Thomas M. Best, Aleksandra E. Zgierska, Eva Zeisig, Michael Ryan, and David Crane. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet-rich plasma. British journal of sports medicine 43, no. 7 (2009): 471-481.


Rabago, David, Aleksandra Zgierska, Luke Fortney, Richard Kijowski, Marlon Mundt, Michael Ryan, Jessica Grettie, and Jeffrey J. Patterson. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. The Journal of Alternative and Complementary Medicine 18, no. 4 (2012): 408-414.

Rabago, David, Jeffrey J. Patterson, Marlon Mundt, Richard Kijowski, Jessica Grettie, Neil A. Segal, and Aleksandra Zgierska. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. The Annals of Family Medicine11, no. 3 (2013): 229-237.

Reeves, Kenneth D., and Khatab Hassanein. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Alternative therapies in health and medicine 6, no. 2 (2000): 68-80.

Reeves, K. Dean, and Khatab Hassanein. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. The Journal of Alternative & Complementary Medicine 6, no. 4 (2000): 311-320.

Reeves, K. Dean, Bradley D. Fullerton, and Gaston Topol. Evidence-based regenerative injection therapy (prolotherapy) in sports medicine. The Sports Medicine Resource Manual. Saunders (Elsevier) (2008): 611-619.

Scarpone, Michael, David Rabago, Aleksandra Zgierska, J. Arbogest, and Edward Snell. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine 18, no. 3 (2008): 248.

Schwartz, Robert G., and Noreen Sagedy. Prolotherapy: A literature review and retrospective study. J Neurol Orthop Med Surg 12, no. 3 (1991): 220-223.

Shallenberger, Frank, and ABAAM HMD. Prolozone™–Regenerating Joints and Eliminating Pain. Journal of Prolotherapy 3, no. 2 (2011): 630-638.

Topol, Gastón Andrés, K. Dean Reeves, and Khatab Mohammed Hassanein. Efficacy of dextrose prolotherapy in elite male kicking-sport athletes with chronic groin pain. Archives of physical medicine and rehabilitation 86, no. 4 (2005): 697-702.

Yelland, Michael J., Paul P. Glasziou, Nikolai Bogduk, Philip J. Schluter, and Mary McKernon. Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial. Spine 29, no. 1 (2004): 9-16.

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