Effect Of Intrathecal Administration Of Adrenomedullin On Mechanical Pain Threshold And Its Neurobiological Mechanisms In Rats

Adrenomedullin(AM),a member of the calcitonin gene-related peptide(CGRP)family,has been recently demonstrated to be a pronociceptive mediator.AM is expressed in superficial laminae of the spinal cord and small-as well as medium-diameter neurons in dorsal root ganglia(DRG).AM induces its biological activities by acting on AM receptor.Previous studies have shown that acute and chronic intrathecal administration of AM can induce thermal hyperalgesia,but it is not clear whether it can induce mechanical allodynia.The increase.in sensitivity to tactile stimulus is main manifestation of neuropathic pain.This study examined the effect of intrathecal administration of AM on tactile threshold and its neurological mechanisms.Methods and purposes:(1)AM1-50,an agonist of AM receptor,was injected intrathecally.The changes of mechanical threshold in rats were examined to determine whether the enhancement of AM receptor activity could induce the change of mechanical pain perception.(2)Intrathecal injection of AM1-50 was done to study the expression of nNOS,p-ERK,GFAP and Ibal proteins in spinal dorsal horn by Western blot.The ppurpose was to explore the mechanism of underlying AM-induced mechanical allodynia.(3)Effect of AM on TRPV1 expression in cultured DRG was determined by Western blot.Results:(1)Intrathecal injection of AM1-50 increased sensitivity responding to stmilus.(2)Intrathecal injection of AM1-50 upregulated the expression of p-ERK,nNOS,Ibal and GFAP proteins.(3)AM increased the TRPV1 protein of DRG cultured in vitro.Conclusions:The increased AM activity at spinal level can enhance mechanical pain.sensitivity.The mechanism involved up-regulation of spinal cord nNOS and p-ERK and activatin of microglia and astrocytes.AM can increase TRPV1 expression in cultured DRG.