Understanding Inflammation in Injury
Ross Hauser, M.D. Marion Hauser, M.S.,R.D.

Local versus Systemic Inflammation
One of the main problems with sports medicine is that ligaments are treated as muscles when they are histologically, functionally, and in many other respects, exactly opposite in nature. Muscles, on one hand, receive more blood supply at rest than any other structure except the lungs, which receive 20 percent of cardiac output. During exercise, muscles receive almost all of the blood supply at 85 percent! Compare this to ligaments whose blood supply is essentially non-measurable.

When it comes to sports injuries and inflammation, the same principle applies. Physicians have been taught that systemic whole-body inflammation is bad and must be suppressed because it could damage the organs and tissues of the body. Good examples of this are rheumatoid arthritis, in which whole body inflammation attacks all of the joints, and systemic lupus erythematosus, which attacks the lungs, heart, and about every other organ of the body. Systemic inflammation has been implicated as the cause of  diabetes, Alzheimer's disease, autism, heart disease, irritable bowel disease, and cancer.

In systemic inflammatory conditions such as these, if the inflammation is not suppressed the condition will continue to deteriorate. Modern medical practitioners sometimes give Prednisone (steroid) and/or anti-inflammatory medications to help deter the inflammation.

Because we practice Prolotherapy and have been taught not to suppress inflammation, we try to find out what is causing the systemic inflammation. We then treat that condition, such as an infection or food allergy. After this is done, the systemic inflammation subsides. The point here is that systemic inflammation is bad for the body, but just suppressing it does not make sense. Always try to find the cause of the inflammation.

Modern medicine, however, has forgotten that local inflammation is good and necessary for healing. Imagine a surgeon opening an abdomen to remove an inflamed appendix and then giving the person anti-inflammatory medications/shots for pain. One hour after the operation the person would be in excruciating pain because of the surgery and the surgeon is going to give the person cortisone injections at the surgical site? Why don't they do this? Would this not be a good way to eliminate the pain of the surgical site? Cortisone injections into the surgical site are not done because they would stop the healing of the area and the wound would dehisce (come open).

Local inflammation is the process by which the body heals the wound after the surgery. What is the patient told to do after surgery? Take some narcotic pain pills and start walking. Why? The patient will be fine in a couple of days if this is done. It is crucial that the staples or stitches keep the wound closed during the initial healing stages, so it will eventually heal completely.

Local Inflammation and Sports Injuries
As the above surgical example makes sense, you might ask yourself the question, "Well, if post-op patients do not receive anti-inflammatory medications after surgery, why are they so quick to give the injured athlete NSAIDs (nonsteroidal anti-inflammatory medications) and cortisone shots when inflammation is necessary for localized healing? The reason is due to the fact that orthopedic surgeons, athletic trainers, and others in the sports medicine field have forgotten the most important concept in medicine: the body heals locally by inflammation. No inflammation at the site of an infection: no healing and the infection spreads. No inflammation at the site of a bone fracture results in a nonhealing fracture (called non-union). No inflammation at the site of a surgical wound, then the wound dehisces (opens up) and the surgeon is left with a mess. For our purposes, no local inflammation at the site of a sports injury, then no healing for the athlete. Since sports injuries typically involve ligaments and tendons, with an already poor blood supply, local inflammation definitely needs to be encouraged or else the athlete has no chance to heal.

The Local Inflammatory Cascade
Local inflammation at the site of the sports injury is the key for the athlete to achieving complete healing. When the injury actually occurred does not matter. Whether a recent injury or if the injury occurred over 30 years ago, the injury will always heal by inflammation. There is no other way to heal the injury. The key to understanding why anti-inflammatories and cortisone shots are so detrimental to healing, and why Prolotherapy is so helpful, is understanding the local inflammatory cascade.

The healing of ligaments and tendons progresses through a series of three stages: inflammatory, fibroblastic, and maturation. The initial inflammatory phase is the most crucial stage because it involves cleaning up the damaged tissue from the injury, protecting the good tissue that is not injured, and setting the stage for tissue repair.

The sequence of events during the inflammatory phase is as follows:
1. Initial injury
2. Vasodilation of the vessels of the microcirculation leading to increased blood flow
3. A marked increase in vascular permeability to protein
4. Filtration of fluid into the tissue with resultant swelling (edema)
5. Exit of neutrophils (and later, monocytes) from the vessels into the tissues
6. Phagocytosis of the damaged tissue
7. Tissue repair starts

Chemical substances released or generated locally mediate all these events; the most important of which are prostaglandins and leukotrienes. Prostaglandins and leukotrienes are a group of modified fatty acids, which function as chemical messengers. They help control such things as blood clotting, immune functioning, and blood circulation at a local cellular level. They appear to be made in all cells of the body.

Prostaglandins and leukotrienes are made when the fatty acids in membranes (the outside of cells) are broken down by an enzyme called phospholipase A2. This forms arachidonic acid, the precursor compound to prostaglandins and leukotrienes. Prostaglandins are formed by the enzyme cyclo-oxygenase and leukotrienes by the enzyme lipoxygenase.

Both prostaglandins and leukotrienes are a class of compounds known as eicosanoids. Eicosanoids are actually hormone-like substances that, unlike normal hormones, are secreted in the blood to go to their target cell. These regulate cell-to-cell activity (paracrine) or even act upon the secreting cell itself (autocrine).

The key to eicosanoids is that they work locally. From this perspective, eicosanoids can be viewed as "master switches" that regulate physiological function at the cellular level. The main eicosanoids involved in local tissue inflammation and repair are those made from arachidonic acid, namely prostaglandins and leukotrienes.

The main function of these groups of eicosanoids is to promote local vasodilation, platelet aggregation, cellular proliferation, and the overall inflammatory response.

It is this initial inflammatory response which will ultimately heal the athlete's soft tissue injury.

Most athletic injuries involve damage to the collagen that makes up the ligaments and tendons. Collagen is one of the strongest known stimulators of platelet clotting. (Robbins, S. Pathologic Basis of Disease. Third Edition. Philadelphia, PA: W. B. Saunders Co., 1984, p. 40-84.)

Platelets are small cells, which adhere to the injured collagen fibers in the presence of midsubstance ligament and tendon tears. This helps stabilize the tear or injury. The platelets also release chemicals, such as histamine, serotonin, and bradykinins, which increase vascular permeability.

This response by the platelets is reinforced by eicosanoids, which are released by the injured cells. The prostaglandins and leukotrienes released initiate vasodilation in the noninjured blood vessels.

They also help attract other immune cells to the area. This allows the filtration of fluid-containing nutrients and immune system cells, which start the clean-up process. These immune cells, including neutrophils, monocytes, and platelets, also release more eicosanoids and further enhance the inflammatory process. (Bucci, L. Nutrition Applied to Injury Rehabilitation and Sports Medicine. Boca Raton, FL: CRC Press, 1995, pp. 1-31.)

This infiltration of fluid and cells leads to the edema, redness, and pain that is common with sports injuries involving torn tendons and ligaments.

All of the above takes place in the athlete immediately after the injury and will continue for about the next seven days. This is the key time for the athlete to receive appropriate treatment.

Receiving treatment immediately after an injury will allow and even aid the inflammatory stage, which improves the chances for complete healing. Anything that increases this local inflammatory reaction will increase the chances of healing. Likewise, treatments and medications that decrease this inflammatory process cause an increased likelihood of a non-healed ligament or tendon. Because this acute swelling is painful for the athlete, the athletic trainer and team physician's natural reactions are to go for the tape, the braces, and the initiation of the RICE treatments to decrease the pain, swelling, and edema.

The athlete must realize that edema is a normal and important part of the healing process. Too little edema can slow the healing process. (Smillie, I. Injuries of the Knee Joint. Baltimore, Maryland: Williams & Wilkins, 1970, p. 130.)

To put it simply, too little edema means too little inflammation to induce healing. It is a well known fact, that rest, ice, compression, and elevation decrease the edema, thereby decreasing healing. In contrast, Movement, Exercise, Analgesics, and Treatments like Prolotherapy encourage edema by stimulating inflammation and thereby aid healing.