Objective: To explore the effects of extracellular signal-regulated protein kinase 5 signaling pathway in chronic constriction injury (CCI)-induced neuropathic pain above spinal cord level.

Methods: The CCI model of neuropathic pain was established. Intracerebroventricular injection of antisense oligonucleotides and immunohistochemical labeling technique were employed. And the heat and mechanical hyperalgesia responses were used to examine the affect of ERK5 in CCI-induced neuropathic pain and the expression of p-CREB (cAMP response-element binding protein) in spinal cord.

Results: The mechanical paw withdrawal reflex threshold and thermal reflex latency became significantly lower in CCI-induced mice. Compared with saline group, mechanical and thermal hyperalgesia significantly decreased and the expression of p-CREB protein decreased at spinal cord in oligonucleotide group.

Conclusions: The ERK5 spinal cord neurons are involved in the regulation of CCI-induced neuropathic pain in mice. And this effect is achieved by adjusting the CREB-dependent gene expression.