Nitric Oxide, Chronic Joint Inflammation, and Pain

Publisher Summary This chapter reviews some basic concepts of NO biology that provide an understanding of the role that NO may play in the pathophysiology of chronic joint inflammation and pain perception. Rheumatoid arthritis (RA) is a chronic systemic disease of unknown etiology characterized by symmetric polyarticular inflammation of synovia-lined joints, remarkable joint swelling, deformation, and pain. Chronic pain is one of the most serious symptoms associated with RA and affects the quality of life of the patients. Prominent histopathological features of the chronically inflamed synovia include neovascularization, hyperemia, infiltration of large numbers of leukocytes, and bone and cartilage degradation. Coincident with this extensive inflammatory infiltrate is the enhanced expression of the inducible isoform of nitric oxide synthase (iNOS) and the sustained overproduction of the free radical, nitric oxide (NO). NO modulates the inflammatory response directly or indirectly and plays an important role in pain perception. Therefore, there is increasing interest in defining the role that it may play in the pathogenesis of RA and chronic pain.