Aim:To investigate whether activation and translocation of extracellular signal-regulated kinase(ERK)is involved in the induction and maintenance of neuro-pathic pain,and effects of activation and translocation of ERK on expression ofpCREB and Fos in the chronic neuropathic pain.Methods:Lumbar intrathecalcatheters were chronically implanted in male Sprague-Dawley rats.The left sciaticnerve was loosely ligated proximal to the sciatica’s trifurcation at approximately 1.0mm intervals with 4-0 silk sutures.The mitogen-activated protein kinase kinase(MEK)inhibitor U0126 or phosphorothioate-modified antisense oligonucleotides(ODN)were intrathecally administered every 12 h,1 d pre-chronic constrictioninjury(CCI)and 3 d post-CCI.Thermal and mechanical nociceptive thresholdswere assessed with the paw withdrawal latency(PWL)to radiant heat and vonFrey filaments.The expression of pERK,pCREB,and Fos were assessed by bothWestern blotting and immunohistochemical analysis.Results:Intrathecal injec-tion of U0126 or ERK antisense ODN significantly attenuated CCI-induced me-chanical allodynia and thermal hyperalgesia.CCI significantly increased the ex-pression of p-ERK-IR neurons in the ipsilateral spinal dorsal horn to injury,not inthe contralateral spinal dorsal horn.The time courses of pERK expression showedthat the levels of both cytosol and nuclear pERK,but not total ERK,were in-creased at all points after CCI and reached a peak level on postoperative d 5.CCIalso significantly increased the expression of pCREB and Fos.Phospho-CREB-positive neurons were distributed in all laminae of the bilateral spinal cord and Foswas expressed in laminae I and II of the ipsilateral spinal dorsal horn.Intrathecalinjection of U0126 or ERK antisense ODN markedly suppressed the increase ofCCI-induced pERK,pCREB and c-Fos expression in the spinal cord.Conclusion:The activation of ERK pathways contributes to neuropathic pain in CCI rats,andthe function of pERK may partly be accomplished via the cAMP response elementbinding protein(CREB)-dependent gene expression. Aim: To investigate whether activation and translocation of extracellular signal-regulated kinase (ERK) is involved in the induction and maintenance of neuro-pathic pain, and effects of activation and translocation of ERK on expression of pCREB and Fos in the chronic neuropathic pain. Methods : Lumbar intrathecalcatheters were chronically implanted in male Sprague-Dawley rats. The left sciatic nerve was loosely ligated proximal to the sciatica’s trifurcation at approximately 1.0 mm intervals with 4-0 silk sutures. The mitogen-activated protein kinase kinase (MEK) inhibitor U0126 or phosphorothioate -modified antisense oligonucleotides (ODN) were intrathecally administered every 12 h, 1 d pre-chronic constrictioninjury (CCI) and 3 d post-CCI.Thermal and mechanical nociceptive thresholdswere assessed with the paw withdrawal latency (PWL) to radiant heat and vonFrey filaments The expression of pERK, pCREB, and Fos were both assessed by both Western blotting and immunohistochemical analysis. Results: Intrathecal injec-ti on of U0126 or ERK antisense ODN significantly attenuated CCI-induced me-chanical allodynia and thermal hyperalgesia. CCI significantly increased the ex-pression of p-ERK-IR neurons in the ipsilateral spinal dorsal horn to injury, not inthe contralateral spinal dorsal horn. The time courses of pERK expression showed that the levels of both cytosol and nuclear pERK, but not total ERK, were in-creased at all points after CCI and reached a peak level on postoperative d 5. CCIalso significantly increased the expression of pCREB and Fos. Phospho-CREB-positive neurons were distributed in all laminae of the bilateral spinal cord and Foswas expressed in laminae I and II of the ipsilateral spinal dorsal horn. Intrathecal injection of U0126 or ERK antisense ODN markedly suppressed the increase of CCI-induced pERK, pCREB and c -Fos expression in the spinal cord. Conlusion: The activation of ERK pathways contributes to neuropathic pain in CCI rats, and the function of pERK may partly be incorporated via cAMPresponse elementbinding protein (CREB) -dependent gene expression.