电针抑制炎症性痛敏反应的中枢机制

The project belongs to the basic study of medical neurobiology. It is mainly involve in the neural mechanism of electroacupuncture-evoked inhibition of inflammatory hyperalgesia. The results of the study are as follows:1) It was demonstrated for the first time that intraplantar injection of carrageenan significantly increased the release of 5-hydroxytryptamine (5-HT), dopamine (DA) and their metabolite 5-hydroxyindoleacetic acid (5-HIAA) and homovaniilc acid (HVA), respectively, in spinal dorsal horn and periaqueductal gray (PAG). The peak occurred 2-3 h after carrageenan injection and then gradually returned to baseline.2) Activity of 5-HT1A and 5-HT1B receptor significantly increased C-responses and post-discharge in most of the wide dynamic range (WDR) neurons. Following carrageenan induced inflammation, the activity of 5-HT1A and 5-HT1B receptor-induced facilitatory effect on C-responses and post-discharge was markedly enhanced. It suggests that 5-HT1A and 5-HT1B receptor subtypes mediate the facilitation of 5-HT on nociceptive processing in the spinal cord of rats. It was found for the first time that the expression of 5-HT1A and 5-HT2A receptor mRNA in the PAG, dorsal raphe nucleus (DRN), nucleus raphe magnus (NRM) and spinal dorsal horn were obviously enhanced following carrageenan. Also, 5-HT1A but 5-HT2A receptor in the PAG, DRN and NRM was demonstrated to be auto-receptors. However, some 5-HT1A receptors in dorsal horn in spinal cord were distributed in GABA and ENK neurons..3) It was indicated that DA system in spinal cord and brain was involved in the central modulation of peripheral inflammatory pain mediated by DAD1 and DAD2 receptors. DAD1 receptor perhaps related to the development of hyperalgesia, and DAD2 receptor exerted anti-hyperalgesic effects, but also tonically inhibited the nociceptive information. It was found for the first time that the expression of D1 and D2 receptor mRNA in the striatum （CPU），PAG, dorsal raphe nucleus (DRN), nucleus raphe magnus (NRM) and spinal dorsal horn were obviously enhanced following carrageenan. Some D2 receptors in CPU and dorsal horn in spinal cord were distributed in ENK neurons. In NRM，some D2 receptors were distributed in 5-HT neurons。.4) It was indicated that IL-1b in spinal cord and brain was involved in the central modulation of peripheral inflammatory pain mediated by IL-1R。 IL-1b in brain may related to the development of hyperalgesia，while IL-1b in spinal cord exerted anti-hyperalgesia。It was found for the first time that the expression of IL-1b and IL-1R1 mRNA in the PAG, dorsal raphe nucleus (DRN), nucleus raphe magnus (NRM) and spinal dorsal horn were obviously enhanced following carrageenan. Some IL-1R1 mRNA in NRM and dorsal horn in spinal cord were distributed in 5-HT and ENK neurons，respectively..5) It was demonstrated for the first time that microinjection of orphanin FQ (OFQ) into PAG significantly facilitated C-responses and post-discharge of WDR neurons in spinal dorsal horn by electrophysiological techniques. Moreover, microinjection of OFQ into NRM markedly increased the tail-flick latency (TFL) in rats, whereas microinjection of OFQ into NGC decreased the TFL, suggesting the analgesia of OFQ in the NRM and the hyperalgesia of OFQ in the NGC..6) It was demonstrated for the first time that excitatory amino acid receptor antagonists in spinal and electroacupuncture can synergetically inhibit inflammatory behavioral hyperalgesia and spinal fos expression。Also，spinal IL-1b markedly enhanced electroacupuncture-evoked anti-hyperalgesia。7) It was demonstrated for the first time that OFQ in NRM can potentiate eletroacupuncture analgesia，whereas OFQ in NGC can antagonize electroacupuncture analgesia。Microinjection of OFQ into PAG and simultaneous electroacupuncture，extracellular concentration of Glu was significantly decreased，whereas extracellular concentration of GABA，5-HT and MHPG were significantly increased。 This may be one of the mechanisms of OFQ in the PAG antagonizing electroacupuncture analgesia。.

从整体、细胞和分子水平等多个层次揭示下行易化系统的活动增强以及下行易化和抑制系统相互作用的力度消长是炎症性痛敏产生的脊髓上基础；不同强度的电针可以通过调整下行易化和抑制系统的机能状态来缓解和减弱炎症性痛敏反应.阐明该机制将为发展针灸学的现代砺圩鞒龉毕祝⑽形饕浇岷咸岣呗酝吹牧俅擦菩峁┬碌睦砺垡谰荨