Mechanisms of Neuropathic Pain

Abstract

Neuropathic pain arises as a direct consequence of a lesion or a disease affecting the somatosensory system. The mechanisms of neuropathic pain are often complex and difficult to study given the diversity of causes, pathology, and clinical presentation of various neuropathic pain conditions. Common mechanisms include peripheral and central sensitizations. Peripheral sensitization refers to increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields. Central sensitization refers to the augmented response of central signaling neurons. The mechanisms of peripheral and central sensitization are understood at the cellular and molecular levels. The processes of neuroplasticity involve activation of inflammatory cells, such as macrophages (and microglia in the central nervous system) and other immune cells, and release of inflammatory mediators, such as cytokines, chemokines, and a host of other mediators. Interactions of these mediators with specific receptors in the nociceptors or the spinal cord neurons may lead to phosphorylation or changes in expression of ion channels, receptors, transporters, and other effectors through specific signaling pathways. These events ultimately lead to changes in excitability, conductivity, and transmissibility of neurons in the pain processing pathways. Other factors may include disinhibition of interneurons, changes in descending inhibitory and excitatory pathways, and reorganization of the cortical areas and their interconnections.