Effect Of DRG On Spinal Dorsal Horn Neurological Changes Evoked By Chronic Morphine In Rats

Morphine is widely used in the treatment of pain,but long-term repeatedly morphine can cause morphine tolerance and severely limit its clinical application,so the mechanism of morphine tolerance is a hot spot of clinical studies.Intrathecal injection of MrgC receptor agonist can alleviate morphine tolerance hyperalgesia or allodynia,and AM receptor also plays an important role in the formation and maintenance of morphine tolerance.This suggests MrgC and AM receptors can be used as a therapeutic target of morphine tolerance.In this study,After Rats subcutaneously injected for 5 consecutive days of morphine,MrgC receptor agonist BAM8-22 and AM receptor antagonist AM22-52 were injected directly into the exposed L3-L5 dorsal root ganglion,an hour later,the cellular modulation mechanism of MrgC receptor and AM receptor in morphine tolerance are explored by immunehistochemistry and Western blot.The results are as follows:in morphine-tolerant rats,the spinal cord dorsal horn astrocytes are activated,IL-1? and CGRP expression are up-regulated,an increase of p-ERK and p-CREB protein expression;DRG injection of BAM8-22 can inhibit activation of astrocytes,IL-1? and CGRP up-regulation in spinal dorsal horn.Injection of AM22-52 is also capable of inhibiting the expression of the above factors,the inhibition of spinal cord dorsal horn CREB signaling pathway,thereby inhibiting the occurrence of morphine tolerance.These results indicate that:the activation of MrgC receptor can inhibit spinal cord dorsal horn astrocytes activation,expression of IL-1? and CGRP,and the inhibition of AM receptor can inhibit the development and maintenance of morphine tolerance by CREB signaling pathways.These results indicate that in the spinal dorsal horn astrocytes,IL-1?,CGRP and ERK,CREB signaling pathways are involved in morphine tolerance.After drugs that can activate MrgC receptor or inhibit AM receptor are injected into DRG,the expression of the above factors are changed.These reveals the mechanism that MrgC receptor activator inhibit morphine tolerance or inhibition of AM receptor is involved in chronic morphine induced morphine tolerance.