Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala
Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala
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慢性压力通过杏仁核中央核中压力影响相关信息与伤害性信息的整合加剧神经性疼痛
DOI：
10.1097/j.pain.0000000000000827
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发表时间：
2017-04-01
期刊：
影响因子：
7.4
通讯作者：
Xing, Guo-Gang
中科院分区：
文献类型：
--
作者：
Li, Ming-Jia;Liu, Ling-Yu;Xing, Guo-Gang
慢性压力导致的疼痛加剧以及疼痛与压力相关的精神疾病（包括焦虑和抑郁）的共病，是重大的临床挑战。然而，其根本机制仍不清楚。在这里，我们研究了慢性强迫游泳应激（CFSS）引起的神经性疼痛的加剧是否是由压力影响相关信息与杏仁核中央核（CeA）中的伤害性信息整合介导的。我们首先证明，CFSS 确实会在大鼠中产生抑郁样行为，并加剧免遭神经损伤 (SNI) 引起的机械性异常性疼痛。此外，我们发现CFSS诱导基底外侧杏仁核（BLA）神经元的敏化和BLA-CeA突触的长时程增强（LTP）的增强，同时，夸大SNI诱导的CeA神经元的敏化和臂旁（PB）-CeA突触的LTP。此外，我们发现CFSS提高了SNI诱导的CeA中含有GluN2B的NMDA（GluN2B-NMDA）受体的功能上调，这被证明是CFSS诱导的PB-CeA突触LTP增强和SNI大鼠疼痛超敏性加剧所必需的。通过抗抑郁药丙咪嗪或艾芬地尔抑制 CFSS 引起的抑郁样行为，可以抑制 CFSS 引起的神经性疼痛的恶化。总的来说，我们的研究结果表明，CFSS 增强了 BLA-CeA 通路的突触效率，导致 GluN2B-NMDA 受体的激活和 CeA 神经元的敏化，随后促进 PB-CeA 通路的疼痛相关突触可塑性，从而加剧 SNI 诱导的神经性疼痛。我们得出的结论是，慢性压力通过将压力影响相关信息与脑区伤害性信息整合而加剧神经性疼痛。
Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats. Moreover, we revealed that CFSS induces both sensitization of basolateral amygdala (BLA) neurons and augmentation of long-term potentiation (LTP) at the BLA-CeA synapse and meanwhile, exaggerates both SNI-induced sensitization of CeA neurons and LTP at the parabrachial (PB)-CeA synapse. In addition, we discovered that CFSS elevates SNI-induced functional up-regulation of GluN2B-containing NMDA (GluN2B-NMDA) receptors in the CeA, which is proved to be necessary for CFSS-induced augmentation of LTP at the PB-CeA synapse and exacerbation of pain hypersensitivity in SNI rats. Suppression of CFSS-elicited depressive-like behaviors by antidepressants imipramine or ifenprodil inhibits the CFSS-induced exacerbation of neuropathic pain. Collectively, our findings suggest that CFSS potentiates synaptic efficiency of the BLA-CeA pathway, leading to the activation of GluN2B-NMDA receptors and sensitization of CeA neurons, which subsequently facilitate pain-related synaptic plasticity of the PB-CeA pathway, thereby exacerbating SNI-induced neuropathic pain. We conclude that chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the CeA.