Nonsteroidal Antiinflammatory Drugs in Tendinopathy: Friend or Foe

Tendinopathy, a broad term used to describe disorders in and around tendons, 1,2 is associated with repetitive tensile forces exerted on tendons. Rapid increases in the duration and intensity of these forces may cause tendon injuries, possibly the starting point in the pathogenesis of chronic tendinopathy. The exact incidence of chronic tendinopathy is unknown given the vast population of professional and recreational athletes suffering from this condition at different anatomic sites. Studies on incidence of tendinopathies are usually site or sport specific, and only provide an approximation of the magnitude of the problem faced by musculoskeletal and sports medicine clinicians in treating this disorder. In addition, a large number of sedentary subjects develop tendinopathy with no apparent history of increased physical activity. Disorganized, haphazard healing, with frayed, separated, and otherwise disrupted collagen fibrils, are features of tendinopathy. These lesions are characterized by the absence of inflammatory cells and a poor healing response. Age-related tendon changes, and not just mechanical overload, may thus play a role in the pathogenesis of tendinopathy, although the exact etiologic, pathophysiologic, and healing mechanisms are still unknown. Gene expression studies have shown an absence of any inflammatory process in chronic Achilles tendinopathy. Microdialysis experiments have shown no evidence of intratendinous chemical inflammation, with prostaglandin E2 (PGE2) levels being normal in chronic tendinopathies. Microdialysis has also shown higher levels of glutamate, an excitatory neurotransmitter and a potent modulator of pain in the central nervous system, in tendinopathic tendons compared with normal tendons. The same technique reveals that the local concentration of lactate in the tendinopathic Achilles tendon is almost twice that of the normal Achilles tendon. It is possible that there is an ischemic component in the pathogenesis of tendinopathy. Ischemia may precede the start of tendinopathy, but examination of tendinopathic lesions reveals neovascularization and increased blood flow in the affected area of the tendon. Neovascularization may be a response to a primary injury or may be the result of a metabolic disorder. It is possible that anaerobic conditions exist in areas of tendinopathy that have a poor blood supply, and are the primary cause of neovascularization. Neovessels and their accompanying nerves, may be responsible for the pain in the tendinopathic tendon, which would account for the success of local injection of sclerosants such as Polidocanol in the management tendinopathy. Chronic tendinopathy may well be the final manifestation of a long-standing metabolic process in which inflammation, although an initiator, does not participate in the final histopathologic and biochemical features of chronic tendinopathy. It is important in understanding this hypothesis to recall the mechanism of tendon healing. A tendon heals by undergoing inflammatory (1–7 days of injury), proliferative (7–21 days), and remodeling (3 weeks–1 year) phases. Despite collagen maturation and remodeling, tendons are biochemically and metabolically less active than bone and muscle. Type III collagen synthesized by fibroblasts in the proliferative phase is gradually replaced by type I collagen from days 12 to 14, with a progressive increase in tensile strength.