Glutamate Receptor Mechanisms Of Sensitization Of Hypothalamic Arcuate Nucleus Neurons In Inflamed Rats

Objective: To explore the glutamate receptor mechanisms and signal transduction of central sensitization in hypothalamic arcuate nucleus (ARC) during peripheral inflammatory pain.Methods: The model of inflamed rats was induced by complete Freund’s adjuvant (CFA); the spontaneous discharge of ARC neurons and their response to noxious stimulation were recorded extracellularly with glass microelectrode; the role of ionotropic glutamate receptors including their NR2B subunit and post-receptor kinase phosphorylation was studied by intracerebroventricular(i.c.v.) injection of MK-801 (non-competitive NMDA receptor antagonist), Ro25-6981 (selective blocker of NMDA receptors containing the NR2B subunit), CNQX (non-NMDA receptor antagonist), PP2 (Src protein tyrosine kinase inhibitor) and GF109203X (protein kinase C inhibitor).Results: (1) The spontaneous discharge frequency of ARC neurons in CFA rats was significantly higher than that in normal rats. (2) The response to noxious stimulation of ARC neurons in CFA rats was significantly higher than that in normal rats. (3) The response to noxious stimulation of ARC nociceptive specific (NS) neurons in CFA rats and normal rats was inhibited after i.c.v. injection of MK-801(20nmol), Ro25-6981(6nmol) and CNQX(20nmol). (4) The response to noxious stimulation of ARC nociceptive specific (NS) neurons in normal rats and CFA rats was inhibited after i.c.v. injection of PP2(5nmol) and GF109203X(0.04nmol).Conclusions: (1) ARC neurons are sensitized and their responses to noxious stimulation are enhanced in CFA-inflamed rats. (2) Central NMDA receptor(NR2B-containing NMDA receptor) and non-NMDA receptor are involved in the response to noxious stimulation of ARC NS neurons of the normal rats and CFA rats. (3) Central Src protein tyrosine kinase and protein kinase C may play a role in response to noxious stimulation of the normal rats and CFA rats. (4) In ARC, one of supraspinal pain-modulating centers, might produce central sensitisation in the case of peripheral inflammation.