Discipline of Pharmacology and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Pain Management Research Institute, Kolling Institute of Medical Research, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW, Australia.
Br J Pharmacol. 2020 Jan;177(2):420-431. doi: 10.1111/bph.14877. Epub 2020 Jan 8.
Pain is a subjective experience involving sensory discriminative and emotionally aversive components. Consistent with its role in pain processing and emotions, the amygdala modulates the aversive component of pain. The laterocapsular region of the central nucleus of the amygdala (CeLC) receives nociceptive information from the parabrachial nucleus (PB) and polymodal, including nociceptive, inputs from the basolateral nucleus of the amygdala (BLA). Opioids are strong analgesics and reduce both the sensory discriminative and the affective component of pain. However, it is unknown whether opioids regulate activity at the two nociceptive inputs to the amygdala.
Using whole-cell electrophysiology, optogenetics, and immunohistochemistry, we investigated whether opioids inhibit the rat PB-CeLC and BLA-CeLC synapses.
Opioids inhibited glutamate release at the PB-CeLC and BLA-CeLC synapses. Opioid inhibition is via the μ-receptor at the PB-CeLC synapse, while at the BLA-CeLC synapse, inhibition is via μ-receptors in all neurons and via δ-receptors and κ-receptors in a subset of neurons.
Agonists of μ-receptors inhibited two of the synaptic inputs carrying nociceptive information into the laterocapsular amygdala. Therefore, μ-receptor agonists, such as morphine, will inhibit glutamate release from PB and BLA in the CeLC, and this could serve as a mechanism through which opioids reduce the affective component of pain and pain-induced associative learning. The lower than expected regulation of BLA synaptic outputs by δ-receptors does not support the proposal that opioid receptor subtypes segregate into subnuclei of brain regions.
疼痛是一种主观体验，涉及感觉辨别和情感厌恶成分。杏仁核在疼痛处理和情绪中起着调节作用，调节疼痛的厌恶成分。杏仁核中央核的外侧capsular 区（CeLC）接收来自臂旁核（PB）和多模态的伤害性信息，包括来自杏仁核基底外侧核（BLA）的伤害性和多模态输入。阿片类药物是强镇痛药，可减少疼痛的感觉辨别和情感成分。然而，尚不清楚阿片类药物是否调节杏仁核的两个伤害性传入的活动。
使用全细胞膜片钳电生理学、光遗传学和免疫组织化学，我们研究了阿片类药物是否抑制大鼠 PB-CeLC 和 BLA-CeLC 突触。
阿片类药物抑制了 PB-CeLC 和 BLA-CeLC 突触的谷氨酸释放。阿片类抑制作用是通过 PB-CeLC 突触上的μ受体，而在 BLA-CeLC 突触上，抑制作用是通过所有神经元上的μ受体和一部分神经元上的δ受体和κ受体。
μ 受体激动剂抑制了两个将伤害性信息传递到外侧杏仁核的突触输入。因此，μ 受体激动剂，如吗啡，将抑制 CeLC 中 PB 和 BLA 的谷氨酸释放，这可能是阿片类药物减少疼痛的情感成分和疼痛诱导的联想学习的一种机制。δ 受体对 BLA 突触输出的调节低于预期，这并不支持阿片受体亚型在脑区的亚核中分离的假说。
