Activation of p-38α MAPK contributes to neuronal hyperexcitability in caudal regions remote from spinal cord injury

In the present Study, we examined whether activation of p-38 alpha MAPK modulates mechanical allodynia and neuronal hyperexcitability, and if propentofylline (PPF, a glial modulator) modulates specifically localized activated p-38 alpha MAPI( expression in caudal regions remote from a low thoracic hemisection injury in rats. T13 spinal hemisection produces bilateral mechanical allodynia in hindpaws with evoked (in response to mechanical stimuli) neuronal hyperexcitability in lumbar spinal wide dynamic range (WDR) neurons compared to Sham Controls. The mechanical allodynia and the evoked activity of WDR neurons is attenuated by intrathecal and topical administration of SB203580, an inhibitor of p-38 MAPK activation dose, dependently (*p<0.05); however, the spontaneous activity showed no significant differences compared to sharn controls. After T13 spinal hemisection, significantly increased phosphorylated (activated form) p-38a MAPK expression was present in both superficial and deep dorsal horn neurons as well as in microglia, but not in astrocytes, in the lumbar spinal cord compared to sham controls (*p<0.05). Intrathecal application of PPF significantly attenuated the expression of phosphorylated p-38 alpha MAN in superficial dorsal horn neurons (10 mM) and in microglia (1 and 10 mM) in the lumbar spinal cord compared to the hemisection group (*p<0.05). In conclusion, our present data demonstrate that activated neuronal and microglial, but not astrocytic, p-38 alpha MAPK contributes to the maintenance of neuronal hyperexcitability in caudal regions following spinal Cord injury. (C) 2009 Elsevier Inc. All rights reserved.