A Role For Adrenomedullin In Neuropathic Pain And Underlying Mechanisms

Background:Adrenomedullin(AM),a new inflammatory mediator,belongs to calcitonin gene-related peptide(CGRP)family.This peptide was firstly extracted from human phaeochromocytoma.It consists of 52 amino acid.AM is distributed in the spinal dorsal horn and the peptide and non-peptide neurons in dorsal root ganglia(DRG).Recent studies have demonstrated that AM is associated with inflammatory pain and morphine tolerance.Neuropathic pain by nerve injury could impact patients’ life quality.In the current study,we will investigate the involvement of AM in the pathogenesis of neuropathic pain by examining the temporal and spatial changes of AM,effect of AM receptor on mechanical allodynia and underlying cellular mechanism.Method:(1)Establishing neuropathic pain rat model by ligating L5 spinal nerve.Behavioural test,immunofluorescence and qPCR techniques were used to examine the temporal and spatial patterns of AM or AM receptor component RAMP2 following nerve injury.(2)Antagonism of AM receptor inhibited the nerve injury-induced mechanical allodynia and CGRP mRNA expression in the spinal dorsal horn.Results:(1)SNL increased expression of AM and/or AM mRNA in nerve,DRG and spinal dorsal horn.It also induced the increase RAMP2 and RAMP2 mRNA in DRG.(2)The present study demonstrated that daily injection of AM22-52 for 7 days reversed SNL induced mechanical allodynia and also abolished the increase in CGRP mRNA expression in the spinal dorsal horn following L5 SNL ligation.Conclusion:Increased AM and RAMP2 expressions in nerve,DRG and/or spinal dorsal horn were involved and in neuropathic pain.The increase AM receptor signaling contributed to the maintenance of neuropathic pain and this contribution was partly ascribed to the increase of CGRP mRNA in the spinal dorsal horn.