Remember the ankle sprain you got playing football back in high school? Isn’t that the ankle that always hurts, even if you do a ton of calf raises? What about the car accident years ago that caused such severe whiplash that you still have neck and back pain? Advancements in surgical procedures have allowed worn-out joints to be replaced and ligaments to be reconstructed and replaced, but what about non-invasive solutions for chronic pain? Well if that pain is the result of stretched and loose connective tissue, the medical community might have an answer for you in a procedure called prolotherapy. Prolotherapy has the potential to allow injured joints, tendons and ligaments to heal without surgical intervention. Endorsed by C. Everett Koop, former surgeon general of the United States, and Detroit Lions’ football players David Sloan and Johnnie Morton, prolotherapy is becoming more popular and mainstream.

What’s Prolo?
Prolotherapy is an injection technique that claims to help the connective tissue of the body heal itself and subsequently reduce pain. It is also referred to as nonsurgical reconstructive therapy or proliferant therapy. The treatment is touted to cure many different types of musculoskeletal pain including arthritis, back and neck pain, fibromyalgia, sports injuries, and carpal tunnel syndrome. The word prolotherapy was coined by George Hackett, MD in 1956 from the Latin word “proli” which means offspring, and “proliferate” which means to produce new cells in rapid succession (1). He describes his medical definition as the “rehabilitation of an incompetent structure by the generation of new cellular tissue.” He conducted 1600 experimental case studies with people before backing up his anecdotal reports with animal studies.

Anatomy Review
Connective tissue binds cells together to form tissues, organs and systems and provides the mechanical links between bones at joints (ligaments) and between muscles and bones (tendons) (2). Connective tissue is composed of elastin and collagen fibers and ground substance. Elastin fibers are elastic and return to their original shape when they are stretched, just like a rubber band. Collagen fibers are virtually inextensible and are extremely strong in comparison to elastin fibers. They are commonly described as being similar in shape, strength, and elasticity to a shoelace (2). And like shoelaces, they can break. Ground substance is the glue that holds it all together. Tendons and ligaments are considered collagenous or fibrous tissue. When they are overstretched, they break. If the tension is released and they do not break, they will stay at the stretched length and not rebound back to the original length. It is this laxity that causes joints to become hypermobile or allow more movement than they are supposed to. This excessive movement can cause irritation, pain, and often disability.

Injuries and Healing
So what exactly happened to your ankle on that fateful football day? After you tripped over your lineman’s foot, the ligaments holding the bones together and the tendons that were connecting the muscles to those bones stretched and possibly tore. Many cells died because of the trauma. That led to an inflammation response inside your ankle. Inflammation is the body’s reaction to an irritant or injury (3). To decrease the inflammation and repair the damage, the injured tissue went through many processes. For it to become stronger yet not form a scar, a balancing act between motion, stress and immobilization was needed. Inadequate blood supply and insufficient nutrition to the injury can also delay or prevent tissue healing.
The above scenario is similar to what happened to professional football players Johnnie Morton and David Sloan. Sloan sustained a turf toe injury and has been through surgery, acupuncture, and other injection techniques for 2 years before trying prolotherapy. He says that he has noticed some pain relief and increase in function after prolotherapy, but isn’t sure if it is due to the injections or a combination of all the treatments. “I certainly believe that with any injury you must exhaust all of the possibilities, not just the mainstream ones, and that alternative treatments can be incorporated into what is traditionally accepted in modern medicine,” Sloan explains. Morton experienced more positive results in his thumb. Just two injections a week apart gave him his first pain-free football season in years.

How Prolo Heals
Prolotherapy injections are composed of many different substances, depending on the injection site and the diagnosis. Usually an anesthetic like lidocaine combined with irritants such as dextrose (sugar water), phenol, glycerine, or sodium morrhuate (a purified derivative of cod liver oil) are used. Animal studies have shown that sodium morrhuate increases ligament and tendon mass, thickness, and strength where it attaches to the bone (4, 5). One critique of these studies, however, is that the experiments were conducted on healthy, not injured tissue. The substances are injected where the tendon or ligament attaches to the bone. It is at this fibrous-osseous union where sprains, strains and tears occur. Here the nerve supply is plentiful and the blood supply for nourishment is not. The injection causes a localized inflammation in these areas, which stimulates the tissue to repair itself. It does not cause stretching or tearing of tissue, like an original traumatic injury. Many claim that Hippocrates first used a version of this technique, but Hackett accredits Jaynes of St. Louis who in 1832 injected hernias with a “sclerosing solution” to produce strong tissue that wouldn’t bulge where it wasn’t supposed to. Sclerotherapy is still used to treat varicose veins.
Prolotherapy treatment sessions differ according to the type of injury and the size of the area needing treatment. Marc Darrow, MD, JD, QME and owner of Joint Rehabilitation & Sports Medical Center in Los Angeles explains that many prolotherapy injections are simply trigger point injections being done near the fibrous-osseous junction. “Trigger points, as described by Travell and Simons in their 1983 landmark book, are considered to be hyperirritable-painful bundles of muscle fibers. When pressed, they can often refer pain to other areas of the body. Ligaments & tendons can also be pain generators. I often use a local anesthetic and dextrose for trigger point injections and for prolotherapy. “ What Dr. Darrow often finds is that pain may be reduced or eliminated by one or two injections and this is before any proliferation of collagen can occur. Therefore he claims that prolotherapy is often simply trigger point therapy. George Hackett, the “founder” of prolotherapy, agrees that both local and referred pain can stem from ligaments (1). Research has also shown that dextrose injections alone can improve knee and hand osteoarthritis and tighten lax anterior cruciate ligaments (6, 7). Generally injections are given 4-6 times with 1-2 weeks in between to allow time for the growth of the new tissue, but some patients may need more, and some may see immediate results. Prolotherapy treatments can range from $100-$250 per visit. In comparison, a surgical outpatient procedure usually starts at about $10,000. Insurance companies seem to be divided on reimbursement, but will frequently cover trigger point injections.

Positive Points
There is quite a bit of scientific research that points to prolotherapy’s efficacy. However two of the most cited studies on prolotherapy’s effectiveness with low back pain are often the two most criticized (8, 9). Although the studies showed very positive results in both reduction of pain and decrease in disability, critics point to the fact that the studies had methodology flaws and were performed by the same investigators. Nevertheless, other case reports and studies have shown favorable effects (10, 11) and one low back study showed through tissue biopsy that no scar tissue was formed and that larger and thicker fibers in the ligaments were produced (12). Other studies have investigated prolotherapy injections for osteoarthritis and knee ligament laxity with encouraging results (6, 7, 13).

Prolo Popularity – Mixed Messages
So if prolotherapy is such an effective treatment and the cost is so low compared to surgery, why isn’t it more popular? Prolotherapy is primarily taught in osteopathic medicine schools where doctors focus on natural and non-invasive methods of treatment as opposed to most medical schools where doctors focus on pharmaceuticals and surgery to cure problems. The procedure requires special training, textbook-perfect anatomy knowledge, and could take up to one hour of clinic time for one patient – time most doctors just do not have. Also our society tends to look for a "quick fix," but prolotherapy might require multiple sessions and devotion to exercise to help heal and keep the joint healthy. Although bodybuilders are used to this type of dedication, many people are not. The most plausible reason that prolotherapy hasn’t helped everyone’s aches and pains, says Dr. Darrow, is that pharmaceutical companies are not promoting it because there is no money in it for them. “Prolotherapy solutions contain substances that are natural and easily obtained. Drug companies cannot make a profit on that.”

Pondering Prolo?
Some procedures practiced thousands of years ago, like leeching, have currently come back into everyday treatment practice. Although the body does a miraculous job of healing itself, medical knowledge perfected throughout the ages has given us innovations to improve and expedite the healing process. It is common practice for orthopedic surgeons to create bleeding sites on bones to promote healing, so why not inject irritants to stimulate new tissue growth? As far as the dangers, not since the 1950s when poor techniques left 3 people paralyzed and 2 dead (14, 15) have there been any reports of serious complications. Prolotherapy should only be performed by experienced practitioners who have been trained in the procedure. If you are considering prolotherapy injections, see “Where to Go For Prolotherapy Information.” For many people, prolotherapy can diminish years of pain.

References:
1. Hackett, G., Ligament and Tendon Relaxation Treated by Prolotherapy. First ed. 1956, Springfield: Charles C. Thomas.
2. Watkins, J., Structure and Function of the Musculoskeletal System. 1999, Champaign: Human Kinetics.
3. Arnheim, D. and W. Prentice, Principles of Athletic Training. Ninth ed. 1997, St. Louis: McGraw-Hill Companies, Inc.
4. Liu, Y., et al., An in situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength. Connective Tissue Research, 1983. 11: p. 95-102.
5. Maynard, J.A., et al., Morphological and biochemical effects of sodium morrhuate on tendons. J Orthop Res, 1985. 3(2): p. 236-248.
6. Reeves, K.D. and K. 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. Journal of Alternative & Complementary Medicine, 2000. 6(4): p. 311-320.
7. Reeves, K.D. and K. Hassanein, Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Alternative Therapies in Health & Medicine, 2000. 6(2): p. 68-74, 77-80.
8. Klein, R.G., et al., A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. Journal of Spinal Disorders, 1993. 6(1): p. 23-33.
9. Ongley, M.J., et al., A new approach to the treatment of chronic low back pain. Lancet, 1987. 2(8551): p. 143-146.
10. Bourdeau, Y., Five-year follow-up on sclerotherapy/prolotherapy for low back pain. Manual Medicine, 1988. 3(4): p. 155-157.
11. Peterson, T.H., Injection Treatment for Back Pain. The American Journal of Orthopedics, 1963. 5(11): p. 320-321, 325.
12. Klein, R., T. Dorman, and C. Johnson, Proliferant injections for low back pain: Histological changes of injected ligaments and objective measurements of lumbar spine mobility before and after treatment. J Neurolo Orthop Med Sur, 1989. 10(2): p. 123-126.
13. Ongley, M.J., et al., Ligament instability of knees: a new approach to treatment. Manual Medicine, 1988. 3: p. 152-154.
14. Keplinger, J. and P. Bucy, Paraplegia from treatment with sclerosing agents. Journal of the American Medical Association, 1960. 173(12): p. 1333-1335.
15. Hunt, W. and B. WC, Complications following injection of sclerosing agent to precipitate fibro-osseous proliferation. Journal of Neurosurger, 1961. 18(4): p. 461-465.