Central neuron-glia interactions and neuropathic pain: overview of recent concepts and clinical implications.

Eduardo E. Benarroch, MD Neuropathic pain results from injury or disease causing dysfunction at any level of the somatosensory (primarily spinothalamic) system, including peripheral nociceptive axons, dorsal root ganglion (DRG), dorsal horn, spinothalamic pathway, and thalamus. The manifestations of neuropathic pain, including spontaneous pain, hyperalgesia, and thermal and mechanical allodynia, reflect excessive excitability of peripheral nociceptors (peripheral sensitization), central nociceptive neurons (central sensitization), or both. Sensitization reflects maladaptive plastic changes in the nociceptive system that result directly from axonal injury and from the effects of products of inflammation. There is abundant evidence that activation of microglia and astrocytes in the dorsal horn is common and constitutes an important amplification mechanism leading to neuropathic pain in the setting of peripheral nerve or spinal cord injury. Activated glial cells are also involved in sensitization of brainstem and thalamic neurons at a distance from the site of injury. The complex roles of the central glia and its mediators in the mechanisms of neuropathic pain have been extensively reviewed.1-9