Carol A. Cooper, Ph.D., Karen K. Brown, Ph.D.,
Chris D. Meletis, N.D., and Nieske Zabriskie, N.D.
Hyaluronic acid (HA) has been known for more than 70 years, but the focus has been on its physical properties— as a replacement for the vitreous humor of the eye, as a lubricant in the joints, or as a humectant in high-end cosmetics. More recently, HA has been recognized as having anti-inflammatory properties, and the molecular weight of the molecule has been established as an important feature of the molecule. HAs of higher molecular weight (HMW) tend to be anti-inflammatory, whereas those of lower molecular weight (LMW) tend to be proinflammatory. It has also been found that LMW fragments of HA, as well as the proinflammatory molecules they generate, stimulate the genes that encode HA synthase, thereby yielding more HA with a preference for the HMW form of this essential molecule.1–3 Overwhelming evidence now suggests that HA functions as a biologically endogenous anti-inflammatory molecule, resolving both acute and chronic inflammation in vivo.4
Structure of HA
HA is a naturally occurring biopolymer belonging to a class of compounds known as glycosaminoglycans (GAGs). In addition to HA, GAGs also include chondroitin sulfate, dermatin sulfate, keratin sulfate, heparin, and heparan sulfate. HA is the only GAG that is nonsulfated. Molecules of HA consist of repeating units of Nacetylglucosamine and glucuronic acid, and these polymers can range in size from 5000 to 20,000,000 Daltons (Da).
Causes of Pain and Swelling
Inflammation is a defensive reaction of the body in response to harmful stimuli, such as pathogens, damaged cells, or irritants. Two of the primary characteristics of inflammation are pain and swelling. In the biologic process known as the leukocyte adhesion cascade (see
Fig. 1), the leukocytes are directed to the site of trauma in order to allow for repair of damage to tissue.5 With trauma, proinflammatory
cytokines are produced, the most important of which are interleukin-
1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF),6 and interferon. 7 These cytokines activate the endothelium of the blood vessels in the affected area. The endothelium expresses cellular adhesion molecules (CAMs) that recruit circulating leukocytes to the surface of the endothelium, where they “roll” to the site of injury. This rolling is accomplished by the successive attachment and release of the leukocyte to the endothelium via cell surface receptors.