The Conduction Mechanism Of MC4R Mediates Neuropathic Pain

Objective: To investigate the influence between melanocortion 4 recepter(MC4R) and NF-κB in spine and DRG which come from chronic constrict injury model,Then inqure into the relation between melanocortion 4 recepter and NF-κB.Methods: Male Wistar which are weighing 180g-200 g were used in this study,the neuropathic pain model was induced by chronic constrict injury(CCI) to sciatic nerve.All the rats were randomly divided into four groups after the rats were successfully intrathecally catheterized assigned to CCI or sham surgery.These foure groups,sham group,only to expose the sciatic nerve and not get surgical ligation;CCI group,expose the sciatic nerve with 4 loose ligatures on the sciatic nerve by 4-0 silk suture at 1mm intervals.H group,CCI+HSO14(MC4 Rantagonist),10ug/day,for seven days.group P,CCI+PDTC(NF-κB inhibitor)2ug/day,for seven days.Measuring Thermal Threshold before operation and on the 3rd,7th and 14 th day after CCI.The level of NF-κB and MC4 R in lumber spinal and dorsal root ganglion(DRG) was tested by western blot and immunohistochemistry.Results: The thermal threshold in CCI group was obviously lower than sham group with operation(p<0.01),MC4 R, NF-κB expression of CCI group in DRG and spinal cord was obviously higher than sham group(p<0.01).Intrathecal administration of HSOI4 OR PDTC evidently blocked the CCI-induced hyperalgesia and HS014 decresed the expression of MC4 R,NF-ΚB in DRG and spinal cord 9(p<0.05)And at the same time,PDTC only decreased the PDTC(P<0.05) but not the MC4 R.Both MC4 R and NF-κB were located in neurons of DRG and located in the same cells in spinal cord.Conclusion: The mechanisms of neuropathic pain is that HS014 decrease the neuropathic pain related to the inbitition of NF-κB activation,and at the same time NF-κB may be a downstream of MC4 R.in the neuropathic pain.induced by CCI.