Effects Of DRG Injection Of AM_22-52 On Chronic Morphine-induced NNOS,Iba1 And CX3CL1 In The Spinal Dorsal Horn

Morphine is currently the best analgesic drug.However,the long-term use of opioids will make the tolerate,seriously restrict its clinical application.Intrathecal administration of AM receptor antagonists relieve morphine tolerance hyperalgesia and hyperalgesia,suggest that AM receptors play an important role in morphine tolerance and maintenance.Pain is caused by peripheral stimulation by afferent nerve,DRG,spinal cord,in the spread to the thalamus,the cerebral cortex receives the signal to feel the pain.Chronic use of morphine,change the plasticity DRG and spinal cord,stimulate DRG in the AM receptor,changes in DRG neurotransmitters,pain media and other excitatory information increased,the signal continues to pass into the spinal cord to maintain the plasticity of the spinal cord changes.AM is a novel morphine mechanism of morphine tolerance,the effect of AM receptors on spinal cord in DRG,and the role of morphine tolerance.In this study,rats were treated with morphine tolerance for 5 days after subcutaneous morphine injection.DRG was injected with AM22-52 for one hour.The expression of AM receptor in DRG was investigated by behavioral and WB The cellular mechanism.The results are as follows:1.rats after chronic administration of morphine,DRG injection of AM22-52 after morphine tolerance inhibition;2.rat DRG injection of AM induced spinal dorsal horn microglia activation and nNOS and CX3CL1 expression;3.rat chronic administration of morphine,DRG injection of AM22-52 inhibition of chronic application of morphine induced spinal dorsal horn microglia activation;also inhibited nNOS and CX3CL1 expression;These results suggest that rat spinal dorsal horn microglia,nNOS and CX3CL1 and other factors involved in morphine tolerance,rat DRG injection inhibition of AM receptor,inhibition of chronic morphine-induced spinal dorsal horn microglia activation;inhibition The expression of nNOS and CX3CL1 was up-regulated.The results suggest that AM receptor is involved in the mechanism of morphine-induced morphine tolerance induced by chronic administration of morphine.AM receptors can serve as a new target in morphine tolerance studies.