Inhibition of glutamatergic transmission by morphine in the basolateral amygdaloid nucleus reduces pain-induced aversion

Abstract We examined the role of glutamatergic transmission within the basolateral amygdaloid nucleus (BLA) in pain-induced aversion using a conditioned place paradigm and an in vivo microdialysis technique in rats. Microinjection of MK-801 (1 or 10 nmol/side) into the bilateral BLA 5 min before intraplantar injection of formalin dose-dependently attenuated formalin-induced conditioned place aversion (F-CPA) without affecting nociceptive behaviors, such as lifting, licking, and biting. On the contrary, microinjection of neither CNQX (30 nmol/side) nor AP-3 (30 nmol/side) showed any significant effect on F-CPA. Microdialysis experiments revealed that intraplantar injection of formalin induced an increase in the extracellular glutamate level within the BLA. This increase in glutamate was suppressed by morphine perfusion (100 mM) via the microdialysis probe. Moreover, intra-BLA injection of morphine (10 mg/side) 5 min before formalin injection attenuated F-CPA without affecting nociceptive behaviors. These results suggest that glutamatergic transmission via NMDA receptors in the BLA plays a crucial role in the paininduced aversion, and that in addition to the well-characterized effects on the sensory component of pain, morphine also influences the affective component of pain through an inhibitory effect on intra-BLA glutamatergic transmission.