Study On The Receptors And Signal Transduction Pathways Involved In The Mechanism Of Electroacupuncture In Adjuvant Arthritis Rats

Objective:To observe the effects of analgesia and immunoloregulation ofelectro-acupuncture and intracerebroventricular（icv.） injection of adenosine A₁receptoragonist CCPA and antagonist DPCPX on CFA-induced arthritis inflammatory pain model（AA） rats，and explore the mechanism of adenosine A₁receptor taking part in thepathological process of inflammatory pain and the effects of acupuncture analgesia andAnti-inflammatory. To observe the expression of adenosine A₁receptor,5-HT_1Areceptor,Guanine nucleotide-binding proteins（G proteins）, mitogen-activated protein kinase（MAPK）in the hypothalamus and spinal cord of AA rats, and preliminary discuss the centralmechanism of related receptors and signal transduction pathways involved inelectro-acupuncture.Methods:AA rats were used as the subjects of the study.By using methods ofbehavioral threshold of pain test and enzyme linked immunosorbent assay（ELISA）, weobserved the influence of pain threshold and the level of IL-1β, IL-12in serum on AA ratsaccording to EA jiaji points or icv. CCPA and DPCPX. By using methods ofimmunohistochemistry and real time PCR, we observed the expression of adenosine A₁receptor,5-HT_1Areceptor, G protein and MAPK in hypothalamus and spinal cord of AArats. Moreover, we observed the influence of EA on the AA rats with these tested index.Results:1.The results of pain threshold indicated that EA could increase the pain threshold, icv.CCPA could increase it and enhance the analgesic effects of EA, while DPCPX couldreduce the pain threshold in AA rats and simultaneously turn over the analgesic effects ofEA.2.The level of IL-1β, IL-12in serum were raised in AA rats. EA and icv. CCPA could reduce the contents of IL-1β, IL-12in serum, while DPCPX increased them and turnedover the anti-inflammatory effects of EA.3.The expressions of ADORA₁in hypothalamus and spinal cord of AA rats werelower than the normal group. EA could up-regulate the expression of the receptor. Icv.CCPA could up-regulate it and enhance the effects of EA, while DPCPX down-regulated itand simultaneously restrained the effects of EA.4.The expressions of5-HT_1Areceptor in hypothalamus and spinal cord of AA ratswere higher than the normal group. EA could down-regulate the expression of5-HT_1AR.5.The expressions of Gi mRNA in hypothalamus and spinal cord of AA rats werehigher than the normal group，while Gs mRNA were lower than the normal one.EA couldregulate the balance of Gi and Gs protein.The expressions of p38and JNK inhypothalamus and spinal cord of AA rats were higher than the normal group.EA coulddown-regulate the expression of them.Conclusions:ADORA₁may be one of the important targets on inflammatory pain andacupuncture analgesia. The central mechanism of the effects of acupuncture analgesia andanti-inflammatory may be related to ADORA₁,5-HT_1AR, as well as the signal transductionpathway mediated by the Gi/Gs protein, P38-MAPK, JNK-MAPK.