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吗啡注射到终纹床核腹侧部对大鼠疼痛的情感成分而不是感觉成分具有抑制作用。

Suppressive effects of morphine injected into the ventral bed nucleus of the stria terminalis on the affective, but not sensory, component of pain in rats.

机构信息

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.

Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.

出版信息

Eur J Neurosci. 2018 Jan;47(1):40-47. doi: 10.1111/ejn.13776. Epub 2017 Dec 8.

Abstract

Pain is a complex experience with both sensory and affective components. Clinical and preclinical studies have shown that the affective component of pain can be reduced by doses of morphine lower than those necessary to reduce the sensory component. Although the neural mechanisms underlying the effects of morphine on the sensory component of pain have been investigated extensively, those influencing the affective component remain to be elucidated. The bed nucleus of the stria terminalis (BNST) has been implicated in the regulation of various negative emotional states, including aversion, anxiety and fear. Thus, this study aimed to clarify the role of the ventral part of the BNST (vBNST) in the actions of morphine on the affective and sensory components of pain. First, the effects of intra-vBNST injections of morphine on intraplantar formalin-induced conditioned place aversion (CPA) and nociceptive behaviors were investigated. Intra-vBNST injections of morphine reduced CPA without affecting nociceptive behaviors, which suggests that intra-vBNST morphine alters the affective, but not sensory, component of pain. Next, to examine the effects of morphine on neuronal excitability in type II vBNST neurons, whole-cell patch-clamp recordings were performed in brain slices. Bath application of morphine hyperpolarized type II vBNST neurons. Thus, the suppressive effects of intra-vBNST morphine on pain-induced aversion may be due to its inhibitory effects on neuronal excitability in type II vBNST neurons. These results suggest that the vBNST is a key brain region involved in the suppressive effects of morphine on the affective component of pain.

摘要

疼痛是一种具有感觉和情感成分的复杂体验。临床和临床前研究表明,吗啡剂量低于降低感觉成分所需的剂量即可降低疼痛的情感成分。尽管已经广泛研究了吗啡对疼痛感觉成分的影响的神经机制,但影响情感成分的机制仍有待阐明。终纹床核(BNST)被认为参与了各种负面情绪状态的调节,包括厌恶、焦虑和恐惧。因此,本研究旨在阐明腹侧 BNST(vBNST)在吗啡对疼痛的情感和感觉成分的作用中的作用。首先,研究了 BNST 腹侧注射吗啡对足底福尔马林诱导的条件性位置厌恶(CPA)和伤害性行为的影响。BNST 腹侧注射吗啡可降低 CPA 而不影响伤害性行为,这表明 BNST 腹侧内吗啡改变了疼痛的情感成分,而不是感觉成分。接下来,为了研究吗啡对 II 型 vBNST 神经元兴奋性的影响,在脑切片中进行了全细胞膜片钳记录。吗啡的浴液应用使 II 型 vBNST 神经元超极化。因此,BNST 腹侧内吗啡对疼痛诱导的厌恶的抑制作用可能是由于其对 II 型 vBNST 神经元兴奋性的抑制作用。这些结果表明,vBNST 是参与吗啡对疼痛情感成分的抑制作用的关键脑区。

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