Invented in the 1950s by George Hackett, prolotherapy is based on the theory that chronic pain is often caused by laxness of the ligaments that are responsible for keeping a joint stable. When ligaments and associated tendons are loose, the body is said to compensate by using muscles to stabilize the joint. The net result, according to prolotherapy theory, is muscle spasms and pain.

Prolotherapy treatment involves injections of chemical irritant solutions into the area around such ligaments. These solutions are believed to cause tissue to proliferate (grow), increasing the strength and thickness of ligaments. In turn, this presumably serves to tighten up the joint and relieve the burden on associated muscles, stopping muscle spasms. In the case of arthritic joints, increased ligament strength would allow the joint to function more efficiently, thus reducing pain.

Prolotherapy has not been widely accepted in conventional medicine. The technique is used by prolotherapy practitioners to treat many conditions, including back pain, osteoarthritis, fibromyalgia, plantar fasciitis, sciatica, sports injuries, temporomandibular joint disorder (TMD), tendinitis, and tension headaches. Most studies have focused on its use in back pain and osteoarthritis, but this evidence does not clearly support its effectiveness.

Prolotherapy is generally administered at intervals of 4 to 6 weeks, although studies have used a more frequent schedule. The treatment involves injection of a mixture containing an irritant and a local anesthetic. A total of 4 to 6 treatments is typical.

When treating back pain, prolotherapy practitioners frequently use a form of manipulation somewhat similar to chiropractic. However, it is applied after local anesthetic has been injected and is somewhat intense.

There are several irritant solutions used in prolotherapy. Concentrated dextrose or glucose has become increasingly popular because it is completely non-toxic. Phenol (a potentially toxic substance) and glycerin are also sometimes used. Other non-irritant substances may be added to the solution, such as vitamin B 12, corn extracts, cod liver oil extracts, zinc, and manganese; however, there is no evidence that these substances add any benefit.