Department of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Anesthesiology, Huizhou Central People's Hospital, Huizhou, China.
Neurobiol Dis. 2024 Nov;202:106699. doi: 10.1016/j.nbd.2024.106699. Epub 2024 Oct 10.
Top-down projections transmit a series of signals encoding pain sensation to the ventrolateral periaqueductal gray (vlPAG), where they converge with various incoming projections to regulate pain. Clarifying the upstream regulatory hierarchy of vlPAG can enhance our understanding of the neural circuitry involved in pain modulation. Here, we show that a in a mouse model of spared nerve injury (SNI), activation of a circuit arising from posterior paraventricular thalamic nucleus CaMKIIα-positive neurons (PVP) projects to gamma-aminobutyric acid neurons in the rostral zona incerta (ZIr) to facilitate the development of pain hypersensitivity behaviors. In turn, these ZIr neurons project to CaMKIIα-positive neurons in the vlPAG (vlPAG), a well-known neuronal population involved in pain descending modulation. In vivo calcium signal recording and whole-cell electrophysiological recordings reveal that the PVP→ZIr→vlPAG circuit is activated in SNI models of persistent pain. Inhibition of this circuit using chemogenetics or optogenetics can alleviate the mechanical pain behaviors. Our study indicates that the PVP→ZIr→vlPAG circuit is involved in the facilitation of neuropathic pain. This previously unrecognized circuit could be explored as a potential target for neuropathic pain treatment.
自上而下的投射将一系列编码疼痛感觉的信号传递到腹外侧导水管周围灰质（vlPAG），在那里它们与各种传入投射汇聚，以调节疼痛。阐明 vlPAG 的上游调节层次结构可以增强我们对参与疼痛调节的神经回路的理解。在这里，我们表明，在 spared nerve injury (SNI) 的小鼠模型中，源自丘脑后室旁核 CaMKIIα 阳性神经元（PVP）的回路的激活投射到 rostral zona incerta (ZIr) 的γ-氨基丁酸神经元，以促进疼痛超敏行为的发展。反过来，这些 ZIr 神经元投射到 vlPAG（vlPAG）中的 CaMKIIα 阳性神经元（vlPAG），这是一个已知的参与疼痛下行调节的神经元群体。体内钙信号记录和全细胞电生理记录显示，该 PVP→ZIr→vlPAG 回路在持续性疼痛的 SNI 模型中被激活。使用化学遗传学或光遗传学抑制该回路可以缓解机械性疼痛行为。我们的研究表明，PVP→ZIr→vlPAG 回路参与了神经病理性疼痛的促进。这个以前未被认识的回路可以作为治疗神经病理性疼痛的潜在靶点进行探索。
