The Function And Mechanism Of MHC-I In Neuropathic Pain

ObjectiveNeuropathic pain is a disease that exists all over the world,with high incidence and poor treatment effect at present.Therefore,it is very important to study the mechanism of its cause.This study mainly discusses the role and molecular mechanism of MHC CLASS 1 in neuropathic pain.Methods8 weeks old C57BL/6 mice were randomly divided into 4 groups:sham group（Sham）,neuropathic pain group（SNI）,neuropathic pain with negative control virus group（SNI plus NC-LV）,and neuropathic pain with virus group（SNI plusβ2m-LV）.An incision is made at the lateral surface of the right thigh,and the proximal and distal parts of the biceps femoris muscle are separated to expose the sciatic nerve and its three terminal branches.Ligate and clip the tibial nerve and nervus peroneus communis.The Sham group just exposed right sciatic nerve and its branches.After the above operation was completed,the SNI mice in SNI plus NC-LV and SNI plusβ2m-LV group received injections of NC-LV andβ2m-LV into the spinal cords respectively on the same day.The paw mechanical withdrawal threshold（PWMT）was recorded on days 0,3,7,14,21.On the 21^stday,all the mice were sacrificed and the L4-L6 spinal cord were cryopreserved for the further treatment.The immunohistochemical staining was used to detect the co-localization of MHC-I and c-fos,Ca MkⅡ,v Glut2 and GAD in cornu dorsale medullae spinalis.QRT-PCR and western blot were perfprmed to detect the expression of MHC-I Ca MkⅡ,v Glut2 and GAD67 in cornu dorsale medullae spinalis.ResultsAll mice had the same basic PWMT in 0^th day,but from 3^rd day,the PWMT of four groups began to differ.It was lower in SNI group than Sham group from3^rd day to 21^st day and showed a persistent decline in SNI group（P<0.05）.But the results of PWMT in SNI plusβ2m-LV group were higher than SNI plus NC-LV group（P<0.05）.The result of immunohistochemical staining suggested there was colocalization in MHC-I and c-fos,Ca MkⅡ,v Glut2 and GAD67.We found the expression of c-fos was increase in SNI group by compared with Sham group（P<0.05）,but compared with SNI plus NC-LV group it was reduced in SNI plusβ2m-LV group（P<0.05）.For the Ca MkⅡand v Glut2,they also had a co-location relationship with MHC-I and increase in SNI group by compared with Sham group.Compared with SNI plus NC-LV group,MHC-I were reduced in SNI plusβ2m-LV group（P<0.05）.the result of GAD67 showed the co-location relationship with MHC-I,but the expression of it was opposite to MHC-I.ConclusionsThe expression level of MHC-I in spinal dorsal horn of mice with neuropathic pain increased and affected the behavioral results of the mice,suggesting that MHC-I was involved in the regulation of neuropathic pain.MHC-I affect the balance of the nervous system excitability inhibitory by its regulation on Ca MkⅡ,v Glut2 and GAD67,and this leads to an increase in neuronal excitability and a decrease in neuronal inhibition.This condition exacerbates the response to painful stimuli.