Inhibition by dexmedetomidine of the activation of spinal dorsal horn glias and the intracellular ERK signaling pathway induced by nerve injury

Activation of glial cells and the intracellular ERK signaling pathway plays an important role in the development and maintenance of neuropathic pain. As well as neurons, glial cell membranes also express alpha(2)-adrenergic receptors, but the effects of selective activation of these receptors on glial cell activation induced by neuropathic pain have yet to be clarified. We investigated the effects of intraperitoneal (IP) injections of tolerable doses of dexmedetomidine (DEX), a highly selective agonist of alpha(2)-adrenergic receptors, on activation of spinal dorsal root glial cells and the intracellular ERK signaling pathway induced by neuropathic pain. Adult rats that underwent partial sciatic nerve ligation (PNSL) were treated with repeated IP injections of DEX 20 mu g/kg or 40 mu g/kg, and their thermal and mechanical hyperalgesia thresholds were measured. The distribution and morphological changes of rnicroglias and astrocytes were observed by immunofluorescence. Western blot was used to detect changes of glial fibrillary acid protein (GFAP) and pERK expression. Repeated IP injections of DEX 40 mu g/kg for 7 or 14 days markedly reduced the thermal and mechanical hyperalgesia induced by PSNL. In addition, DEX 20 mu g/kg for 14 days and 40 mu g/kg for 7 days also significantly inhibited PSNL-induced activation of pERK in the spinal dorsal horn. Thus, repeated IP injections of DEX can markedly relieve the hyperalgesia of neuropathic pain in rats. The analgesic effect of DEX maybe attributed to its inhibition of glial cell hypertrophy in the spinal dorsal horn and activation of the intracellular ERK signaling pathway. (C) 2011 Elsevier B.V. All rights reserved.