The functional anatomy of neuropathic pain

Neuropathic pain originates from abnormal nociceptive processing at various levels of the pain pathways. The most striking characteristic of neuropathic pain is the loss of selective responsiveness to truly noxious (versus innocuous) stimuli, a phenomenon that is strictly related to a process of sensitization involving a series of receptor and synaptic changes at the peripheral and central levels. Structural changes at the molecular level are translated into functional changes in nociceptive neurons, which produce enlarged receptive fields and aberrant responses to innocuous stimuli. These structural and functional changes can evolve into a process of further sensitization of the pain pathways, including such higher centers as the thalamus and sensorimotor cortex. The result of this process is increased pain perception at the peripheral and central levels and reduced efficacy of the descending modulatory pathways. Many recent reports have detailed the various neurotransmitters and peptides that play a role in triggering and maintaining the process of sensitization that produces chronic neuropathic pain. The purpose of the present report is to briefly review the physiologic organization of the ascending and descending pain pathways and to illustrate some of the mechanisms that may play particular roles in the generation of chronic neuropathic pain.