Mapping the pain pathway: The VPL–S1HL–ACC circuit's role in central post-stroke pain

IF 3.7 3区 医学 Q2 NEUROSCIENCES
Panyang Li , Chaofan Lu , Mingliang Wang , Yuanyuan Mao , Xi Wang , Yi Liu , Jingjing Zhang , Sen Zhao
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引用次数: 0

Abstract

Central post-stroke pain (CPSP) is a chronic neuropathic condition driven by central sensitization, often resulting in poor clinical outcomes. Neural circuits play a critical role in modulating chronic pain. To elucidate the mechanisms underlying CPSP, we established a mouse model via intracranial injection of type IV collagenase. cFos immunofluorescence and in vivo calcium imaging identified pain-associated activated nuclei. Using viral tracing, optogenetics, chemogenetics, and behavioral assays, we mapped a neural circuit comprising the ventral posterolateral thalamic nucleus (VPL), the hindlimb primary somatosensory cortex (S1HL), and the anterior cingulate cortex (ACC). In CPSP mice, ipsilateral S1HLCaMKIIα and ACCCaMKIIα neurons exhibited robust activation. Chemogenetic manipulation further demonstrated that activation of these neurons induced pain behaviors, whereas their inhibition alleviated pain. Notably, specific activation of the S1HLCaMKIIα–ACCCaMKIIα circuit produced mechanical allodynia, and optogenetic stimulation of VPLCaMKIIα projections to S1HL similarly evoked pain responses while enhancing ACC neuronal firing. These findings underscore the critical role of the VPL–S1HL–ACC circuit in pain abnormalities and provide novel insights into the central sensitization underlying CPSP, suggesting promising therapeutic strategies for its management.
绘制疼痛通路:VPL-S1HL-ACC回路在中枢性卒中后疼痛中的作用
中枢性卒中后疼痛(CPSP)是一种由中枢致敏性驱动的慢性神经性疾病,通常导致较差的临床结果。神经回路在调节慢性疼痛中起着关键作用。为了阐明CPSP的机制,我们通过颅内注射IV型胶原酶建立了小鼠模型。cFos免疫荧光和体内钙显像鉴定了疼痛相关的活化核。利用病毒追踪、光遗传学、化学遗传学和行为分析,我们绘制了一个由丘脑腹侧后外侧核(VPL)、后肢初级体感皮层(S1HL)和前扣带皮层(ACC)组成的神经回路。在CPSP小鼠中,同侧S1HLCaMKIIα和ACCCaMKIIα神经元表现出强劲的激活。化学发生操作进一步证明,这些神经元的激活诱导疼痛行为,而它们的抑制减轻疼痛。值得注意的是,S1HLCaMKIIα-ACCCaMKIIα回路的特异性激活产生了机械性异常性痛,而VPLCaMKIIα投射到S1HL的光遗传刺激同样引起了疼痛反应,同时增强了ACC神经元的放电。这些发现强调了VPL-S1HL-ACC回路在疼痛异常中的关键作用,并为CPSP的中枢致敏提供了新的见解,为其管理提供了有希望的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Brain Research Bulletin
Brain Research Bulletin 医学-神经科学
CiteScore
6.90
自引率
2.60%
发文量
253
审稿时长
67 days
期刊介绍: The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.
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