Activation of ERK/CREB pathway in spinal cord contributes to chronic constrictive injury-induced neuropathic pain in rats  

作　　者：Xue-songSONG Jun-liCAO Yan-bingXU Jian-huaHE Li-caiZHANG Yin-mingZENG 

机构地区：[1]DepartmentofAnesthesiology,FirstClinicalCollegeofN.BethuneCentreofHealthSciences,JilinUniversity,Changchun130021,China [2]DepartmentofAnesthesiology,AffiliatedHospitalofXuzhouMedicalCollege,Xuzhou221002,China//JiangsuInstituteofAnesthesiology,Xuzhou221002,China [3]DepartmentofAnesthesiology,AffiliatedHospitalofXuzhouMedicalCollege,Xuzhou221002,China [4]DepartmentofAnesthesiology,AffiliatedHospitalofXuzhouMedicalCollege,Xuzhou221002,China//JiangsuInstituteofAnesthesiology,Xuzhou221002,China

出　　处：《Acta Pharmacologica Sinica》2005年第7期789-798,共10页中国药理学报（英文版）

基　　金：Project supported by an Open Project Grant from the Jiangsu Province Key Laboratory of Anesthesiology(No KSJ03081);the National Natural Science Foundation of China(No 30200267).

摘　　要：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 intrathecal catheters 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 constriction injury(CCI)and 3 d post-CCI.Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal latency(PWL)to radiant heat and von Frey filaments.The expression of pERK,pCREB,and Fos were assessed by both Western 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 in the 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.CCI also significantly increased the expression of pCREB and Fos.Phospho-CREB- positive neurons were distributed in all laminae of the bilateral spinal cord and Fos was 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.Conclusion: The activation of ERK pathways contributes to neuropathic pain in CCI rats,and the function of pERK may partly be accomplished via the cAMP response element bindinAim: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 intrathecal catheters 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 constriction injury(CCI)and 3 d post-CCI.Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal latency(PWL)to radiant heat and von Frey filaments.The expression of pERK,pCREB,and Fos were assessed by both Western 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 in the 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.CCI also significantly increased the expression of pCREB and Fos.Phospho-CREB- positive neurons were distributed in all laminae of the bilateral spinal cord and Fos was 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.Conclusion: The activation of ERK pathways contributes to neuropathic pain in CCI rats,and the function of pERK may partly be accomplished via the cAMP response element bindin

关 键 词：extracellular signal-regulated kinases cyclic AMP-response DNA-binding protein PAIN HYPERALGESIA spinal cord 

分 类 号：R681.5[医药卫生—骨科学]