Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China.
Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, PR China.
Nat Neurosci. 2021 Apr;24(4):542-553. doi: 10.1038/s41593-021-00811-x. Epub 2021 Mar 8.
In humans, tissue injury and depression can both cause pain hypersensitivity, but whether this involves distinct circuits remains unknown. Here, we identify two discrete glutamatergic neuronal circuits in male mice: a projection from the posterior thalamic nucleus (PO) to primary somatosensory cortex glutamatergic neurons (S1) mediates allodynia from tissue injury, whereas a pathway from the parafascicular thalamic nucleus (PF) to anterior cingulate cortex GABA-containing neurons to glutamatergic neurons (ACC) mediates allodynia associated with a depression-like state. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that PO and PF populations undergo different adaptations in the two conditions. Artificial manipulation of each circuit affects allodynia resulting from either tissue injury or depression-like states, but not both. Our study demonstrates that the distinct thalamocortical circuits PO→S1 and PF→ACC subserve allodynia associated with tissue injury and depression-like states, respectively, thus providing insights into the circuit basis of pathological pain resulting from different etiologies.
在人类中，组织损伤和抑郁都可能导致痛觉过敏，但这是否涉及不同的回路尚不清楚。在这里，我们在雄性小鼠中鉴定出两个离散的谷氨酸能神经元回路：来自丘脑后核（PO）的投射到初级体感皮层谷氨酸能神经元（S1）的通路介导了组织损伤引起的痛觉过敏，而来自旁束核（PF）到扣带前皮质 GABA 能神经元到谷氨酸能神经元（ACC）的通路介导了与抑郁样状态相关的痛觉过敏。体内钙成像和多电极电生理记录显示，PO 和 PF 群体在两种情况下经历不同的适应。每个回路的人工操作都会影响组织损伤或类似抑郁状态引起的痛觉过敏，但不会同时影响两种。我们的研究表明，PO→S1 和 PF→ACC 这两个不同的丘脑皮质回路分别介导与组织损伤和抑郁样状态相关的痛觉过敏，从而为不同病因引起的病理性疼痛的回路基础提供了深入了解。
