Histological analyses of CRF mRNA expression in the dorsolateral bed nucleus of the stria terminalis of chronic pain model rats

We previously reported that VTA-projecting dorsolateral bed nucleus of the stria terminalis (dlBNST) neurons make synapses onto the VTA GABAergic neurons, suggesting that suppression of these projecting neurons may lead to activation of VTA GABAergic neurons, thereby suppressing VTA dopaminergic neurons. Recently, using electrophysiological analyses, we found the increased inhibitory inputs to VTA-projecting dlBNST neurons mediated by enhanced CRF signaling in the dlBNST of chronic pain model rats. CRF production has been reported to be produced in both intrinsic neurons within the dlBNST and the neurons projecting from the central amygdala to the dlBNST. Therefore, in this study, CRF mRNA expression in these brain areas of chronic pain model rats was examined by in situ hybridization histochemistry (ISH). CRF mRNA expression was increased in both dlBNST and CeA. In addition, the influence of the enhanced CRF signaling in the dlBNST on VTA dopaminergic neuron activity was examined by ISH and in vivo microdialysis. Injection of CRF type 1 receptor antagonist into the dlBNST of chronic pain model rats increased c-fos mRNA expression in the VTA TH-positive neurons and dopamine release in the nucleus accumbens, indicating the suppression of VTA dopaminergic neuron activity by enhanced CRF signaling in the dlBNST during chronic pain.