Inhibition of noradrenaline release by clonidine in the ventral bed nucleus of the stria terminalis attenuates pain-induced aversion in rats

Pain is an unpleasant sensory and emotional experience. The neural systems underlying the sensory component of pain have been studied extensively, but we are only beginning to understand those underlying the affective component of pain. Previously, we showed the pivotal role of noradrenergic transmission in the ventral part of the bed nucleus of the stria terminalis (vBNST) in the negative affective component of pain using a conditioned place paradigm. In this study, we examined the effect of local administration of clonidine, an α2-adrenoceptor agonist, into the vBNST on noradrenaline release and on conditioned place aversion (CPA) induced by an intraplantar formalin injection in male Sprague-Dawley rats. In vivo microdialysis showed that the formalin-induced increase in the extracellular noradrenaline level within the vBNST was significantly suppressed by clonidine (100 μM) perfusion through a microdialysis probe. Bilateral intra-vBNST injections of clonidine (1 and 10 nmol/side) dose-dependently attenuated formalin-induced CPA without reducing nociceptive behaviors. These results suggest that clonidine inhibits noradrenaline release by acting on α2-adrenoceptors located in the vBNST and thereby attenuates pain-induced aversion. α2-adrenoceptors in the vBNST play a pivotal role in the regulation of negative affective, but not the sensory, component of pain.

► Pain-induced noradrenaline release in the ventral BNST was suppressed by clonidine.
► Intra-vBNST injections of clonidine significantly attenuated pain-induced aversion.
► Intra-vBNST injections of clonidine did not affect nociceptive behaviors.
► 2-adrenoceptors in the vBNST play a pivotal role in the affective component of pain.