The Effect And Mechanism Of BAM8-22 And AM22-52 Inhibit LPS Induced Inflammatory Pain

MrgC receptor belongs to the G protein-coupled receptors and is uniquely located in small and medium-sized neurons of trigeminal and dorsal root ganglia(DRG).It has been demonstrated that MrgC receptor can modulate pain.However,it is unclear whether the MrgC receptor modulates LPS-induced inflammatory pain.Adrenomedullin(AM),a member of the CGRP family,is expressed in superficial laminae of the spinal cord and DRG.Studies have shown that AM is closely related to the induction of pain.However,the role of AM in LPS-induced pain is unknown.In this study,the techniques of behavioral,Western blot,RT-PCR,immunohistochemistry and cell culture were used to explore effect of MrgC receptor on LPS-induced pain and the involvement of AM in LPS-induced pain.Their mechanisms were also investigated.The results show:(1)Intraperitoneal(i.p.)injection of LPS induced decrease in mechanical and thermal pain thresholds(defined as mechanical allodynia and thermal hyperalgesia,respectively).Intrathecal(i.t.)injection of BAM8-22(5 nmol,10 nmol and 20 nmol),the MrgC receptor agonist,inhibited the LPS-induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner.(2)LPS induced up-regulation of GFAP,IL-1β,TNF-α and P2X7 in the cultured DRG.The activation degree of satellite glial cells was dose-dependent with LPS.Application of BAM8-22 concentration-dependently(25 nM,50 nM,200 nM,400 nM)inhibited the LPS-induced increase of GFAP,IL-1β,TNF-α and P2X7 in DRG cultures.(3)AM22-52(AM receptor antagonist)given i.t.inhibited LPS-induced mechanical allodynia and thermal hyperalgesia.The AM22-52-induced changes were dose-dependent(5 nmol,10 nmol,20 nmol).The injection of AM22-52 also inhibited LPS-induced up-regulation of GFAP and P2X7 expressions in DRG in vivo.(4)Application of LPS increase expression of CLR in DRG cultures.AM22-52(5μM,10 μM,20 μM,40 μM)inhibited LPS-induced up-regulation of GFAP,IL-1β,TNF-α,P2X7 and CLR expressions in DRG.The AM22-52-induced inhibition of GFAP was dose-dependent.Conclusions:(1)Activation of MrgC receptor relieved LPS-induced inflammatory pain.This inhibition was ascribed to the inhibition of satellite glial cells in DRG.(2)Activation of AM receptor contributed to LPS-induced inflammatory pain.The mechanisms involved the activation of satellite glial cells in DRG.