The pharmacologic management of neuropathic pain

Abstract

N reuropathic pain intrinsically differs from nociceptive pain. Nociceptive pain is mediated by activation of nociceptors (transduction) a~d transmission of electrochemical impulses along defined pathways to higher rostral centers. Modulation of afferent noxious input occurs at the level of the spinal cord. In contrast, neuropathic pain cannot occur de novo. By definition, the genesis of neuropathic pain implies damage to neural tissue. There are no predefined pathways, but pre-existent pathways may be damaged. Spontaneous discharge of damaged neurons or higher order neurons is responsible for the genesis of neuropathic pain. These changes become permanent because of the plasticity of the central nervous system. Despite these basic differences, nociceptive and neuropathic pain do share certain aspects of the physiologic processes of transduction, transmission, and modulation. While it is not the purpose of this article to exhaustibly review the neuroscience of neuropathic pain, it would be worthwhile to discuss some basic concepts. Nociceptors (nerves that transmit noxious impulses throughout the nervous system) differ from non-nociceptors in two discrete ways: ( I ) they are stimulated at higher threshaids than non-nociceptors, and (2) they have the ability to be sensitized. Sensitization refers to a decrease in the stimulation threshold as well as an increase in the magnitude of the response to that stimulation. Both peripheral and central nociceptors may become sensitized. Much has been written with respect to the central sensitization or wind-up of dorsal horn neurons. Release of excitatory amino acids (glutamate and aspartate) and neuropeptides (substance P, cal-