Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People's Hospital, Anhui Mental Health Center, Hefei, China.
Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Department of Pathology, Anhui Medical College, Hefei, China.
J Biol Chem. 2022 Aug;298(8):102207. doi: 10.1016/j.jbc.2022.102207. Epub 2022 Jun 27.
Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLA) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLA neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (IC) to BLA neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MD) to BLA neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into their paws. Optical inhibition of the IC→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MD→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the IC→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MD→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete IC→BLA and MD→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.
疼痛是一种多维感知，包括不愉快的躯体感觉和情感体验；然而，介导不同疼痛成分的潜在神经回路仍然难以捉摸。尽管外侧杏仁核谷氨酸能（BLA）神经元的过度活跃是躯体感觉和疼痛情绪处理所必需的，但BLA 神经元的精确兴奋性输入及其在介导不同疼痛方面的作用尚不清楚。在这里，我们在雄性小鼠中鉴定了两个离散的谷氨酸能神经元回路：来自岛叶皮质谷氨酸能（IC）到 BLA 神经元的投射，调节疼痛的躯体感觉和情感成分，以及来自中背侧丘脑核（MD）到 BLA 神经元的投射，仅调节疼痛的厌恶情感成分。使用全细胞记录和光纤光度测定法，我们发现，在向爪子注射完全弗氏佐剂（CFA）引起炎性疼痛时，IC→BLA 和 MD→BLA 通路内的神经元在小鼠中被激活。IC→BLA 通路的光抑制增加了 CFA 小鼠的痛觉阈值并诱导了行为性位置偏好。相比之下，MD→BLA 通路的光抑制不影响痛觉阈值，但仍诱导 CFA 小鼠的位置偏好。在正常小鼠中，IC→BLA 通路的光激活降低了痛觉阈值并诱导了位置厌恶，而 MD→BLA 通路的光激活仅引起厌恶。总之，我们的结果表明，离散的 IC→BLA 和 MD→BLA 通路参与调节疼痛的不同成分，为其提供了电路基础的见解，并更好地理解了疼痛感知。
