Prolotherapy

Editors-In-Chief: Robert G. Schwartz, M.D. [mailto:RGSHEAL@aol.com], Piedmont Physical Medicine and Rehabilitation, P.A.; Dean Reeves, M.D., Clinical assistant professor at the University of Kansas Medical School, Dept of Physical Medicine and Rehabilitation; Felix Linetsky, M.D., Clinical Associate Professor, Department of Osteopathic Principles and Practice, Nova Southeastern College of Osteopathic Medicine [mailto:flinetsky@me.com]

Overview
Prolotherapy ("Proliferative Injection Therapy") involves injecting an otherwise non-pharmacological and non-active proliferant or 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. While there is some confilcting evidence, the majority of literature demonstrates its effectiveness and it has enjoyed increasing acceptance within the medical community.

Prolotherapy can be distinguished from sclerotherapy. Sclerotherapy is the use of injections of caustics into the veins, in vascular surgery and dermatology, to remove varicose veins and other vascular irregularities. Prolotherapy is the use of injections in tendons or ligaments to correct connective tissue weakness and reduce musculoskeletal pain. Prolotherapy is also called "proliferation therapy" and "regenerative injection therapy."

Prolotherapy is often used as an alternative to invasive arthroscopic surgery. This is an important alternative, especially when ligamentous structures are involved. The unique role of prolotherapy is highlighted when taking into consideration the effectiveness of arthroscopy. A double-blind placebo-controlled study on arthroscopic surgery for osteoarthritis of the knee was published in the New England Journal of Medicine in July 2002 and concluded that the group that received actual arthroscopic surgery did not report better function or pain than the placebo group."

Arthroscopic surgery of the knee is, however, rarely performed for the indication of osteoarthritis, but rather for mechanical tears or disruptions of cartilaginous tissue. Prolotherapy is not intended to address this type of problem. Doctors and surgeons have given numerous accounts of successful treatment for knee injuries, shoulder separation, and typical injuries to golfers (epicondylitis, shoulder strain, lower back strain and injury, hip and knee injury).

As of April 2005, doctors at the Mayo Clinic began supporting prolotherapy. Robert D. Sheeler, MD (Medical Editor, Mayo Clinic Health letter) first learned of prolotherapy through C. Everett Koop’s interest in the treatment. Mayo Clinic doctors list the areas that are most likely to benefit from prolotherapy treatment: ankles, knees, elbows, and sacroiliac joint in the low back. They report that "unlike corticosteroid injections — which may provide temporary relief — prolotherapy involves improving the injected tissue by stimulating tissue growth."

While identifing a clearly delinated population of back pain patients in the literature can be quite challenging, an evidence-based medicine review of prolotherapy for low back pain concluded: "There is conflicting evidence regarding the efficacy of prolotherapy injections for patients with chronic low-back pain. If used alone, prolotherapy injections do not have a role in the treatment of chronic low-back pain. When combined with other treatments, they may give prolonged partial relief of pain and disability." More studies are currently underway (see Ongoing study section below).

Prolotherapy in clinical practice
Prolotherapy involves the injection of either an irritant or proliferant solution into the area where connective tissue has been weakened or damaged through injury or strain. Many solutions are used, including Dextrose, Lidocaine (a commonly used local anesthetic), Phenol (an alcohol), Glycerine, Cod Liver Oil extract or Sodium Morrhuate. The injection is placed onto ligament, into joint capsules or where tendon connects to bone. Many points may require injection. The Injected solution causes the body to heal itself through the process of inflammation and repair. In the case of weakened or torn connective tissue, induced inflammation and release of growth factor at the site of injury may result in a 40% strengthening of the attachment points.

Most clinicians say that at least three injections, done at 2-3 week intervals, are required to accomplish this result. In addition, patients may receive treatment beyond the initial three injections until treatments are required only every several years, if at all. Allen R Banks, Ph.D., has described in detail the theory behind prolotherapy in "A Rationale for Prolotherapy". Robert G. Schwartz, MD has also published a biochemical literature review on the topic "Prolotherapy: A Literature Review and Retrospective Study".

History
Injections of irritant solutions were performed in the late 1800’s to repair hernias and in the early 1900’s for jaw pain due to temporomandibular (jaw) joint laxity. Dr. George Hackett, MD developed the technique of prolotherapy in the 1940’s. Dr. Gustav Hemwall was a pioneer, beginning his studies and treatments in the 1950s and continuing until the mid 1990s. In his study of almost 10,000 prolotherapy cases, Dr. Hackett found that over 99 percent of the patients found relief from their chronic pain.

Guidelines used by practitioners as indicators for prolotherapy

 * Recurrent swelling or fullness involving a joint or muscular region
 * Popping, clicking, grinding, or catching sensations with movement
 * A sensation of the “leg giving way” with associated back pain
 * Temporary benefit from chiropractic manipulation or manual mobilization that fails to ultimately resolve the pain
 * Distinct tender points and “jump signs” along the bone at tendon or ligament attachments
 * Numbness, tingling, aching, or burning, referred into an upper or lower extremity
 * Recurrent headache, face pain, jaw pain, ear pain
 * Chest pain with tenderness along the rib attachments on the spine or along the front of the chest
 * Spine pain that does not respond to surgery, or whose origin is not clear or consistent based on extensive studies

Evidence based medicine
A Cochrane review of the medical literature as of January 2004 on the efficacy of prolotherapy injections in adults with chronic low-back pain found four controlled trials, all measuring pain and disability levels at six months. The review concluded:


 * "There is conflicting evidence regarding the efficacy of prolotherapy injections in reducing pain and disability in patients with chronic low-back pain. Conclusions are confounded by clinical heterogeneity amongst studies and by the presence of co-interventions." "... in the presence of co-interventions, prolotherapy injections were more effective than control injections, more so when both injections and co-interventions were controlled concurrently."

The review also noted: "[m]inor side effects from the treatment, such as increased back pain and stiffness, were common but short-lived." ("Stiffness" is an expected short-lived side effect, as the goal is to cause irritation and the corresponding body reaction of temporary inflammation and repair.)

More recently Lyftogt J. [Prolotherapy for recalcitrant lumbago. Australasia Musculoskeletal Med. 2008; 13 (5):18-20] published that ninety percent of patients with recalcitrant lumbago reported more then 50% improvement after prolotherapy. Long term follow up results were not stated. In addition, Rabago et al. [A systematic review of prolotherapy for chronic musculoskeletal pain. Clin J Sport Med. 2005 Sep;15(5):376-80] noted: "Two [randomized controlled trials] on osteoarthritis reported decreased pain, increased range of motion, and increased patellofemoral cartilage thickness after prolotherapy."

Criticism
While many major medical insurance policies cover the treatment, not all do. Twenty years ago (After a 1999 review of the medical evidence) Medicare declined prolotherapy coverage for chronic low back pain (citing that prolotherapy "was last examined for coverage by the Health Care Financing Administration (HCFA) in September 1992").

Knee injuries
A randomized, double-blind, placebo control study is currently recruiting patients to determine whether prolotherapy can decrease pain and disability from knee osteoarthritis. This study is Sponsored by the National Center for Complementary and Alternative Medicine (NCCAM).

Tennis elbow
A randomized, double-blind, placebo control study is currently recruiting patients to determine whether prolotherapy can be an effective treatment for lateral epicondylitis (tennis elbow).