Effects Of Adrenomedullin In The Periphery On Europathic Pain

Background:After nerve injury,the excitability of peripheral neurons rises to form peripheral sensitization,which leads to central sensitization,resulting in hypersensitivity of pain.On the other hand,adrenomedullin(AM),participating in the formation of neuropathic pain,is expressed in both NGF-and GDNF-dependent nociceptive neurons in dorsal root ganglion(DRG)and superficial layers of the spinal cord.AM22-52,an AM receptor antagonist,can inhibit the mechanical pain hypersensitivity and heat pain induced by spinal nerve ligation.Aim:to investigate the role of peripheral adrenalmedulla in neuropathic pain.Research methods and content:behavioral test,immunohistochemical fluorescence staining and real-time fluorescent quantitative PCR technology were applied in this study.(1)The establishment of L5 spinal nerve ligation model,the effect of local injection of AM receptor antagonist AM22-52 in peripheral tissues on mechanical pain hypersensitivity and thermal hyperalgesia in rats;(2)the effect of local injection of AM22-52 on the expression of nNOS,CGRP and IL-1β,TNF-a mRNA in DRG induced by spinal nerve ligation;(3)the effect of local injection of AM22-52 on the expression of Iba-1 as well as IL-1β and TNF-a mRNA in the spinal dorsal horn induced by spinal nerve ligation were researched.Results:(1)Local injection of AM22-s2 in peripheral tissues could inhibit the mechanical hypersensitivity and thermal hyperalgesia induced by spinal nerve ligation.(2)The increase of nNOS.and CGRP positive neurons and the up-regulation of IL-1β and TNF-a mRNA in DRG induced by spinal nerve ligation were inhibited by blocking the local AM activity of peripheral tissues.(3)The increase of Iba-1 and the increase of IL-1β and TNF-a mRNA in the spinal dorsal horn caused by spinal nerve ligation were inhibited by blocking the local AM activity of peripheral tissues.This study indicates that increased activity of peripheral AM could change the phenotype of cells in DRG and microglia in the spinal dorsal horn.It was suggested that the increase of peripheral AM activity was a neural mechanism that promoted the formation of peripheral sensitization and central sensitization,and thus participated in the development of neuropathic pain.