RESUMO
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 α(2)-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 α(2)-adrenoceptors located in the vBNST and thereby attenuates pain-induced aversion. α(2)-adrenoceptors in the vBNST play a pivotal role in the regulation of negative affective, but not the sensory, component of pain.
Assuntos
Clonidina/farmacologia , Norepinefrina/antagonistas & inibidores , Norepinefrina/metabolismo , Medição da Dor/efeitos dos fármacos , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/metabolismo , Animais , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Relação Dose-Resposta a Droga , Masculino , Microdiálise , Medição da Dor/métodos , Ratos , Ratos Sprague-DawleyRESUMO
Pain is an unpleasant sensory and emotional experience. We demonstrated the crucial role of the bed nucleus of the stria terminalis (BNST) in the negative affective component of somatic and visceral pain induced by intraplantar formalin and intraperitoneal acetic acid injections, respectively, in rats. Recently, we reported the involvement of enhanced noradrenergic transmission via beta-adrenoceptors within the ventral BNST (vBNST) in formalin-induced aversion. Here, we examined the role of intra-vBNST noradrenergic transmission in the negative affective component of visceral pain induced by intraperitoneal acetic acid injection. In vivo microdialysis showed that extracellular noradrenaline levels within the vBNST significantly increased after intraperitoneal acetic acid injection. Using a conditioned place aversion (CPA) test, we found that intra-vBNST injection of timolol, a beta-adrenoceptor antagonist, dose-dependently attenuated the acetic acid-induced CPA without reducing nociceptive behaviors. These results suggest that enhanced noradrenergic transmission via beta-adrenoceptors within the vBNST plays a pivotal role in the negative affective, but not sensory, component of visceral pain.