Prolotherapy
Prolotherapy is also known as simply prolo, ligament injections, ligament sclerosing injections, ligament reconstruction therapy, or sclerotherapy. This treatment involves the injection of sclerosing agents into connective tissue surrounding injured joints. A similar approach has successfully been used for hernias, hemorrhoids, hydroceles, varicose veins, and other conditions since the 18th century. The goal of this treatment is for the injected solution to induce inflammatory changes in the area of injection, thereby precipitating fibroblastic proliferation and connective tissue growth. In the case of inguinal hernias, this connective tissue growth is thought to be capable of strengthening the local connective tissue and repair small defects causing the hernia. In the case of varicose veins, connective tissue growth is desired to fill the lumen, stop blood flow, and prevent further enlargement of the varicosity. The ideal solution is one that achieves maximum localized fibroblastic proliferation and connective tissue growth with minimal exudate, and minimum discomfort or toxicity to the patient. For this reason, a number of different sclerosing agents have been proposed and used over the past century, including Sylnasol (a polyunsaturated plant fatty acid), zinc sulphate, dextrose, glycerin, phenol, alcohol, and others.
The earliest publication of sclerosing injections for musculoskeletal applications dates from 1937 when Earl H. Gedney, an osteopathic physician, reported using Neo-Plasmoid or MacDonald’s solutions (composition unknown) to inject into hypermobile joints such as the knee or sacroiliac. Since this first report in the 1930s, numerous other physicians have adopted this method of treatment for common musculoskeletal conditions such as low back pain, neck pain, knee pain, hip pain, and other joint pain due to suspected hypermobility or ligament and connective tissue damage. This practice grew significantly in the 1950s due to pioneering research by George Stuart Hackett, a proponent of sclerotherapy for joint pain. Another pioneering physician, Milne J. Ongley, experimented with dozens of different solutions in the 1950s and 1960s before settling on a particular solution he found most beneficial with the least amount of adverse effects. This solution consists of three ingredients found in many pharmaceutical injections: dextrose 25.0%, glycerin 25.0%, and phenol 2.5%. To minimize patient discomfort during the injection procedure and momentarily interrupt the pain with a local anesthetic, Ongley diluted this solution with lidocaine (0.5% or 1%) in a 1:1 ratio, thereby achieving a final product concentration of: dextrose 12.5%, glycerin 12.5%, lidocaine 0.25% or 0.5%, and phenol 1.25% in pyrogen-free water. This combination is known as Ongley's solution or P2G (for phenol, glucose, glycerin).
There is extensive literature support for this form of treatment, though much of this is derived from older, non-controlled, mostly anecdotal reports of success in the 1950s and 1960s. Most of the literature concerning this form of treatment refers to the dextrose/glycerin/phenol/lidocaine solution described above. At least 3 randomized controlled trials have been published using this solution for chronic low back pain. The first 2, conducted by the physicians Ongley, Eek, and Klein at the Sansum clinic in Santa Barbara, California, reported excellent results, though other treatments were included in their treatment approach and thus the effects of prolotherapy alone could not be isolated. The third study was confined to prolotherapy but had only half the number of treatments and one-third the amount of solution used in the 2 previous studies and thus did not report superiority over placebo. Despite the clinical success reported in the literature with this treatment approach and sclerosing solution, little is known about its safety and toxicology. A survey of practitioners seemed to indicate that very few adverse effects had been associated with this treatment, most of which were related to the injection technique itself rather than the solution used. To determine the safety and toxicology of this sclerosing solution in patients with chronic low back pain, a Phase I study is being prepared.