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.

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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.

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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.

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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.

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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.

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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.