Opposing Roles of Corticotropin-Releasing Factor and Neuropeptide Y within the Dorsolateral Bed Nucleus of the Stria Terminalis in the Negative Affective Component of Pain in Rats
Opposing Roles of Corticotropin-Releasing Factor and Neuropeptide Y within the Dorsolateral Bed Nucleus of the Stria Terminalis in the Negative Affective Component of Pain in Rats
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DOI：
10.1523/jneurosci.4278-12.2013
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发表时间：
2013-04-03
影响因子：
5.3
通讯作者：
Minami, Masabumi
中科院分区：
文献类型：
--
作者：
Ide, Soichiro;Hara, Taiki;Minami, Masabumi
疼痛是由感觉和情感成分组成的复杂体验。虽然疼痛的感觉成分的神经系统已被广泛研究，其情感成分的神经系统仍有待确定。在本研究中，我们研究了促肾上腺皮质激素释放因子（CRF）和神经肽Y（NPY）注射到背外侧床核的终纹（dlBNST）对大鼠疼痛引起的厌恶和伤害性行为的影响，以检查这些肽的作用，分别在情感和感觉成分的疼痛。在体内微透析表明，福尔马林诱发的疼痛增强了该脑区CRF的释放。使用条件性位置厌恶（CPA）测试，我们发现，内dlBNST注射CRF 1或CRF 2受体拮抗剂抑制疼痛引起的厌恶。即使在没有疼痛刺激的情况下，dlBNST内注射CRF也诱导CPA。另一方面，dlBNST内注射NPY抑制疼痛引起的厌恶。联合应用NPY可抑制CRF诱导的CPA。NPY的这种抑制作用可被Y-1或Y-5受体拮抗剂阻断。此外，dlBNST切片的全细胞膜片钳电生理学显示，CRF增加神经元的兴奋性，特别是在II型dlBNST神经元，而NPY降低它在这些神经元。CRF对Ⅱ型dlBNST神经元的兴奋作用可被NPY抑制。这些结果揭示了一些潜在的情感成分的疼痛的神经元机制，通过显示相反的作用内dlBNST CRF和NPY在疼痛引起的厌恶和相反的行动，这些肽对神经元兴奋性收敛于相同的目标，II型神经元，在dlBNST。
Pain is a complex experience composed of sensory and affective components. Although the neural systems of the sensory component of pain have been studied extensively, those of its affective component remain to be determined. In the present study, we examined the effects of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) injected into the dorsolateral bed nucleus of the stria terminalis (dlBNST) on pain-induced aversion and nociceptive behaviors in rats to examine the roles of these peptides in affective and sensory components of pain, respectively. In vivo microdialysis showed that formalin-evoked pain enhanced the release of CRF in this brain region. Using a conditioned place aversion (CPA) test, we found that intra-dlBNST injection of a CRF1 or CRF2 receptor antagonist suppressed pain-induced aversion. Intra-dlBNST CRF injection induced CPA even in the absence of pain stimulation. On the other hand, intra-dlBNST NPY injection suppressed pain-induced aversion. Coadministration of NPY inhibited CRF-induced CPA. This inhibitory effect of NPY was blocked by coadministration of a Y-1 or Y-5 receptor antagonist. Furthermore, whole-cell patch-clamp electrophysiology in dlBNST slices revealed that CRF increased neuronal excitability specifically in type II dlBNST neurons, whereas NPY decreased it in these neurons. Excitatory effects of CRF on type II dlBNST neurons were suppressed by NPY. These results have uncovered some of the neuronal mechanisms underlying the affective component of pain by showing opposing roles of intra-dlBNST CRF and NPY in pain-induced aversion and opposing actions of these peptides on neuronal excitability converging on the same target, type II neurons, within the dlBNST.