A Role For Adrenomedullin In Inflammatory Pain By Cfa And Glial Cell Involvement Mechanism

Introduction:Adrenomedullin(AM)belongs to calcitonin gene-related peptide(CGRP)family.And adrenomedullin is a proven neuropeptide involved in pain formation.AM and AM receptors were expressed in the superficial layer of spinal dorsal horn and DRG(an important part of nociceptive information transmission).Studies in other laboratories and our laboratory have shown that intrathecal injection of AM can induce thermal hyperalgesia and mechanical hypersensitivity,suggesting that AM is involved in the transmission of nociceptive information and the formation of hyperalgesia.In this study,complete Freund's adjuvant(CFA)model was used to study the effects of intrathecal injection of AM receptor antagonist AM22-52,on the mechanical behavior of inflammatory pain induced by CFA in rats,and the mechanism of AM regulating peripheral and central glial cells involved in CFA inflammatory pain.Methods and purposes:(1)Whether intrathecal injection of AM receptor antagonist AM22-52 can induce changes in mechanical pain sensation in CFA inflammatory pain rats.(2)Whether AM is involved in the mechanism of early inflammatory pain induced by CFA is related to glial cell activity.(3)Whether AM participates in CFA-induced late inflammatory pain is associated with glial cell activity.Results:(1)The sensitivity of mechanical pain sensation increased on the 2nd and 7th day after CFA inflammatory pain modeling,while intrathecal injection of AM22-52 decreased the sensitivity of mechanical pain sensation in CFA rats.(2)The expression of GFAP,P2X7,TNF-?,IL-1?,p-ERK in dorsal root ganglion and GFAP,Iba1,TNF-?,p-p38 protein in spinal dorsal horn increased on the 2nd day after CFA modeling.Intrathecal injection of AM22-52 could inhibit the expression of these factors in inflammatory pain induced by CFA.(3)The expression of GFAP,P2X7,TNF-? and GFAP,TNF-?,p-JNK protein in DRG and spinal dorsal horn increased in CFA 7-day group,but the expression of Iba1 inspinal dorsal horn did not change.Intrathecal injection of AM22-52 could inhibit the increased expression of GFAP,P2X7,TNF-? in dorsal root ganglion and GFAP,TNF-?and p-JNK in spinal cord in the late stage of inflammatory pain induced by CFA.Conclusions:Intrathecal injection of AM22-52 could inhibit the decrease of mechanical pain threshold induced by CFA in rats,which indicated that AM was involved in CFA-induced inflammatory pain.Intrathecal injection of AM22-52 inhibits activation markers,cytokines,and phosphorylated signaling of spinal dorsal horn astrocytes,microglia,and DRG satellite glial cells in the early(day 2)and late(day 7)of CFA inflammatory pain.The expression of protein was up-regulated.It is suggested that blocking AM receptor may inhibit CFA-induced inflammatory pain by inhibiting glial cell activity.