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.
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.