Neuronal basis for pain-induced aversion

Pain is a complex experience composed of sensory and emotional components. We demonstrated the differential patterns of c-fos mRNA induction by chemical somatic (formalin) and visceral (acetic acid) noxious stimuli in the rat amygdaloid nuclei, the brain regions implicated in emotion. We also showed that conditioned place aversion (CPA) induced by formalin was abolished by the lesion of the basolateral (BLA) or central (CeA) amygdaloid nucleus, while the acetic acid-induced CPA was abolished by the CeA-, but not BLA-, lesion. These results suggest the differential contribution of the BLA and CeA to the negative emotional component of chemical somatic and visceral pain. We demonstrated the critical involvement of intra-BLA glutamatergic transmission via NMDA receptors in formalin-induced aversion. Intra-BLA morphine suppressed this glutamatergic transmission as well as somatic pain-induced aversion. Furthermore, we examined the role of the bed nucleus of the stria terminalis (BST), one of the brain regions forming the extended amygdala. Excitotoxic lesion of the BST as well as intra-BST injection of a beta-adrenoceptor antagonist timolol suppressed the formalin-induced CPA, suggesting that noradrenergic transmission via beta-adrenoceptors within the BST plays an important role in the emotional component of pain.