REVIEW ■ : Pain Mechanisms

Abstract

Over the last few years, a new synthesis has emerged concerning the neural mechanisms of acute and chronic pain. This new model deals far more successfully than do classical models with the peculiarities of chronic pain syndromes seen in the clinic. As in earlier models, Aδ- and C-nociceptive afferents detect the initial noxious event. In addition, however, this input is now known to rapidly trigger a central hyperexcitability state ("central sensitization") that amplifies sensory signals subsequently entering the CNS along other afferent fiber types. As a result, in the presence of central sensitization, pain sensation is evoked by Aβ touch input, as well as by Aδ- and C-nociceptor input. Tenderness in subacute (e.g., inflammatory) pain, for example, is due to both peripherally sensitized nociceptors and centrally amplified, low-threshold input. The new synthesis also stresses the common ground between the subacute pain of injured tissue and the chronic pain that sometimes develops after nerve injury (i.e., neuropathic pain). In the event of neuropathic pain, the affected afferent axons and their sensory cell somata in the associated dorsal root ganglia (DRGs) become hyperexcitable to applied stimuli. Some even fire spontaneously. Hyperexcitability of the afferent neuron apparently results from specific changes in the regulation of membrane channel and receptor proteins. The resulting ectopic discharge (ectopia) contributes a direct neuropathic pain signal. In addition, neuropathic ectopia sets up and maintains a central sensitization state that amplifies ongoing pain and is responsible for pain on weak stimulation of adjacent areas of skin and deep tissues with residual innervation. The discovery that normal and ectopic Aβ touch input, as well as Aδ- and C-nociceptor input, contributes to subacute and chronic pathophysiological pain states opens previously unanticipated avenues for clinical pain control. NEUROSCIENTIST 2:233-244, 1996