Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Neuropharmacology. 2022 Jun 1;210:109031. doi: 10.1016/j.neuropharm.2022.109031. Epub 2022 Mar 15.
The amygdala plays a critical role in the emotional-affective component of pain and pain modulation. The central nucleus of amygdala (CeA) serves major output functions and has been linked to pain-related behaviors. Corticotropin releasing factor (CRF) in the CeA has emerged as an important modulator of pain and affective disorders. Here we measured the effects of optogenetic manipulation of CeA-CRF neurons on pain-related behaviors in a rat neuropathic pain model and under control conditions. Emotional-affective behaviors (vocalizations), mechanosensitivity (electronic von Frey anesthesiometer and calibrated forceps), and anxiety-like behaviors (open field test and elevated plus maze) were assessed in adult rats 1 week and 4 weeks after spinal nerve ligation (SNL model) and sham surgery (control). For optogenetic silencing or activation of CRF neurons, a Cre-inducible viral vector encoding enhanced halorhodopsin (eNpHR) or channelrhodopsin 2 (ChR) was injected stereotaxically into the right CeA of transgenic Crh-Cre rats. Light of the appropriate wavelength (590 nm for eNpHR; 473 nm for ChR) was delivered into the CeA with an LED optic fiber. Optical silencing of CeA-CRF neurons decreased the emotional-affective responses in the acute and chronic phases of the neuropathic pain model but had anxiolytic effects only at the chronic stage and no effect on mechanosensitivity. Optogenetic activation of CeA-CRF neurons increased the emotional-affective responses and induced anxiety-like behaviors but had no effect on mechanosensitivity in control rats. The data show the critical contribution of CeA-CRF neurons to pain-related behaviors under normal conditions and beneficial effects of inhibiting CeA-CRF neurons in neuropathic pain.
杏仁核在疼痛的情感-情感成分和疼痛调节中起着关键作用。杏仁中央核（CeA）主要起输出功能的作用，并与疼痛相关行为有关。CeA 中的促肾上腺皮质激素释放因子（CRF）已成为疼痛和情感障碍的重要调节剂。在这里，我们测量了 CeA-CRF 神经元的光遗传学操作对大鼠神经病理性疼痛模型和对照条件下与疼痛相关行为的影响。在脊髓神经结扎（SNL 模型）和假手术后 1 周和 4 周，对成年大鼠进行情感-情感行为（发声）、机械敏感性（电子 von Frey 麻醉计和校准镊子）和焦虑样行为（旷场试验和高架十字迷宫）评估。对于 CRF 神经元的光遗传学沉默或激活，使用编码增强型盐藻菌视蛋白（eNpHR）或通道视蛋白 2（ChR）的 Cre 诱导病毒载体立体定向注射到 Crh-Cre 转基因大鼠的右侧 CeA 中。适当波长的光（eNpHR 为 590nm；ChR 为 473nm）通过 LED 光纤输送到 CeA。CeA-CRF 神经元的光学沉默降低了神经病理性疼痛模型的急性和慢性阶段的情感-情感反应，但仅在慢性阶段具有抗焦虑作用，对机械敏感性没有影响。CeA-CRF 神经元的光遗传学激活增加了情感-情感反应，并诱导了焦虑样行为，但对对照大鼠的机械敏感性没有影响。这些数据表明 CeA-CRF 神经元在正常情况下对与疼痛相关的行为有重要贡献，并抑制 CeA-CRF 神经元在神经病理性疼痛中的有益作用。
