The NMDA Receptor In Hypothalamic Arcuate Nucleus Participates In The Modulation Of Nociception And Hyperalgesia

The paper is to study the role of N-methyl-D-aspartate receptor (NMDAR) in arcuate nucleus (ARC) in the modulation of nociception in the normal rats and observe the effect of NMDAR in ARC on the regulation of the hyperalgesia in the complete Freund's adjuvant-inflamed (CFA-inflamed) rats.The experimental results indicated that: (1) There was NMDAR-expression in ARC in the normal rats. The pain threshold was increased dose-dependently by microinjection of glutamic acid (Glu) into ARC, showing an analgesic effect. The effect could be mimicked by NMDAR agonist N-methyl-D-aspartate (NMDA) and reversed by its antagonist MK-801. (2) The expression of NMDAR in ARC was up-regulated in the CFA-inflamed rats. The analgesic effect by microinjection of Glu into ARC in the CFA-inflamed rats was stronger and earlier than that in the normal rats. The effect could be reversed by MK-801 with higher dose. (3) The mechanical hyperalgesia and thermal hyperalgesia in the CFA-inflamed rats could be reversed by NMDAR antagonist MK-801, and also be reversed by tyrosine kinase inhibitor PP2.The results suggested that the NMDAR in ARC was involved in the modulation of nociception in the normal rats as well as in the regulation of hyperalgesia in CFA-inflamed rats. It provided the experimental evidence to show that the NMDAR in supraspinal center was involved in central sensitization of hyperalgesia.