Activation of p38 mitogen-activated protein kinase in spinal cord contributes to chronic constriction injury-induced neuropathic pain.

The present study aimed to investigate the role of spinal p38 mitogen-activated protein kinase (p38 MAPK) activation in chronic constriction injury (CCI) of the sciatic nerve induced neuropathic pain. CCI model was produced by loosely ligating the left sciatic nerve proximal to the sciatica's trifurcation with 4-0 silk thread in male Sprague-Dawley rat. SB203580, a specific inhibitor of the p38 MAPK, was intrathecally administered on day 5 post-CCI. Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal lantency (PWL) to radiant heat and the paw withdrawal threshold (PWT) to von Frey filaments respectively. The protein levels of the phosphorylated p38 MAPK (p-p38 MAPK) and phosphorylated cAMP response element binding protein (pCREB) were assessed by Western blot analysis. The results showed that CCI significantly increased the expressions of cytosolic and nuclear p-p38 MAPK in the spinal cord. Intrathecal administration of SB203580 dose-dependently reversed the established mechanical allodynia and thermal hyperalgesia induced by CCI. Correlated with behavior results, SB203580 dose-dependently inhibited the CCI-induced increase of the expressions of cytosolic and nuclear p-p38 MAPK and nuclear pCREB in the spinal cord. Taken together, these findings suggest that the activation of p38 MAPK pathway contributes to the development of neuropathic pain induced by CCI, and that the function of p-p38 MAPK may partly be accomplished via the CREB-dependent gene expression.