The Study Of The Mechanism By Which Melanocortin 4 Receptor Mediates Neuropathic Pain

Objective: To investigate the mechanism by which melanocortin4receptor (MC4R) decrease theneuropathic pain induced by chronic constrict injury (CCI).Methods: Male Wistar rats weighing280-320g were used in this study, The neuropathic pain modelwas established by chronic constrict injury (CCI) to sciatic nerve. After all the rats were successfullyintrathecally catheterized and assigned to CCI or sham surgery. And they were randomly divided intofour groups, sham group, only expose the sciatic nerve without surgical ligation; CCI group, sciaticnerve were exposed and4loose ligatures were placed on the sciatic nerve at1mm intervals with4-0silk suture; H group, CCI+HS014(MC4R antagonist),5ug I day, for seven days; S Group, CCI+SB203580(p38MAPK inhibitor) lOmg/day, for seven days. Thermal Threshold was measured beforeoperation and on the3rd,7th and14th day after CCI. The level of MC4R and phosphorylatedp38MAPK (p-p38MAPK) in dorsal root ganglion and lumbar spinal cord was tested byimmunohistochemistry and p-p38MAPK were also tested by ELISA (enzyme-linked immunosorbentassay) and western blot.Results: The thermal threshold was significantly lower in CCI group than in sham operation group(P<0.01), and MC4R and p-p38MAPK expression in the DRG and spinal cord were significantlyincreased in CCI group vs sham group (p<0.01). Intrathecal administration of HS014or SB203580significantly inhibited the CCI-induced hyperalgesia and HS014decreased the expression of MC4Rand p-p38MAPK (p<0.05) of DRG and spinal cord. But SB203580only decreased the p-p38MAPK(P<0.05) but not the MC4R.Both MC4R and p-p38MAPK were both located in neurons in DRG andlocated in the same cells in spinal cord.Conclusion: The mechanisms of neuropathic pain mediated by MC4R in the DRG and spinal cordmay be related to the inhibition of the p38MAPK activation, p38MAPK may be a downstream ofMC4R.