Peripheral and Central Immune Mechanisms in Neuropathic Pain

Abstract

An injury to the nervous system can be a slight stretch, a compression, or a severe contusion. Such damage usually leads to an acute response characterized by pain, inflammation, and restriction of normal function. However, in about 7-18% of the general population, pain persists, even after the injury heals, producing a state of chronic neuropathic pain. This type of hypersensitivity is debilitating and refractory to the majority of available analgesics. It adversely affects the quality of life and bears a substantial cost to society. In the past two decades, compelling evidence strongly suggested that, in addition to changes in neuronal system, pathogenesis of neuropathic pain involves the bi-directional signaling between the immune system and the nervous system. It has been well established, at least in experimental animal models, that non-neuronal cells, including peripheral immune cells, central nervous system (CNS) glial cells, and endothelial cells, play important roles in the neuroimmune interaction and subsequent persistent hypersensitivity. Various cytokines and chemokines have been identified as key signalling molecules in the crosstalk. Therapeutic agents targeting inflammation provide an exciting prospect. Yet, given the complexity of the immune response to the damage on the nervous system, finely tuned strategies for modulating inflammation are essential to reduce pain while also promoting tissue repair and functional recovery.