PT632. Alteration of the effects of corticotropin-releasing factor on synaptic transmission in the dorsolateral bed nucleus of the stria terminalis of chronic pain model rats

Abstract

Abstract The dorsolateral bed nucleus of the stria terminalis (dlBNST) is densely innervated with corticotropin-releasing factor (CRF) containing fibers. We previously reported that CRF depolarizes typeⅡ neurons and enhances inhibitory synaptic transmission to typeⅢ neurons in the dlBNST. We also demonstrated the critical role of CRF neurotransmission within the dlBNST in aversive responses induced by formalin-evoked pain. However, the roles of CRF within the dlBNST in the regulation of negative emotions under the chronic pain condition remain to be elucidated. In this study, we examined the effects of CRF and a CRF receptor antagonist on the synaptic currents in the dlBNST neurons using the whole-cell patch-clamp recordings. Brain slices including the dlBNST were prepared from chronic pain model rats in which neuropathic pain was induced by spinal nerve ligation (SNL). In sham-operated rats, spinal nerves were exposed without ligation. Bath application of CRF significantly increased the amplitude of evoked excitatory post synaptic current (eEPSC) in typeⅡ neurons of the sham-operated rats, but not of the SNL model rats. By contrast, the amplitude of eEPSC was significantly decreased by bath application of NBI27914 (CRF1 receptor antagonist) in typeⅡ neurons of SNL model rats, but not of the sham-operated rats. Next we examined the spontaneous inhibitory synaptic current (sIPSC) in typeⅢ dlBNST neurons. The frequency of sIPSC in typeⅢ neurons of the sham-operated rats was increased by bath application of CRF, but not of the SNL model rats. Furthermore, the frequency of basal sIPSC in typeⅢ neurons of the SNL model rats was higher than that of the sham-operated rats. These data suggest that neurotransmission via CRF1 receptors within the dlBNST are continuously activated under the chronic pain condition. (283 words)