Contribution of central sensitization to the pain-related abnormal activity in neuropathic rats

Abstract

The possibility of different contributions from peripheral and central sensitization to distinct neuropathic pain syndromes has been studied in rats with chronic constriction of the sciatic nerve (CCI), showing positive behavioral signs of neuropathic pain. In anesthetized, paralyzed rats extracellular recordings were performed in the spinal sciatic afferent territory (L5-L6), ipsilateral to the injured nerve, from wide dynamic range (WDR) neurons. The spontaneous activity and the responses to noxious stimuli applied to the proper area, i.e., the skin innervated by the constricted sciatic nerve, and to "inappropriate" areas, like the tail and the area of skin supplied by the contralateral sciatic and saphenous nerves, were analyzed before and after input from the constricted nerve was reversibly blocked at the ganglionic level by local anesthetic. The neurons discharged spontaneously with high frequencies, and responded to the stimulation of proper and "inappropriate" areas with high frequency discharge and prolonged afterdischarges. During the ganglionic block, confirmed by the lack of responses to proper area stimulation, the WDR neuron background activity was significantly reduced; the responses to all "inappropriate" afferences were present, the frequency discharges being comparable to the preblock ones while the afterdischarges were significantly shorter. Since the efficacy of "inappropriate" inputs is related to neuronal sensitization, the persistence of these responses indicates that central neurons remain sensitized during peripheral block. In view of the relationship between the examined spontaneous and stimulated activities and neuropathic pain symptoms, the data suggest that central sensitization contributes with different drive strength to such symptoms, playing a crucial role in extraterritorial pain.