皮层和部分皮层下结构缺失或躯体感觉皮层功能抑制影响小鼠触觉敏感性和机械痛阈

DEFICIENCY OF CEREBRAL CORTEX AND SOME SUBCORTICAL STRUCTURE OR INHIBITION OF PRIMARY SOMATOSENSORY CORTEX AFFECTS TACTILE SENSITIVITY AND MEAHCNICAL PAIN IN MICE

摘要:

目的：利用基因工程小鼠和化学遗传学手段探究皮层缺失和初级感觉皮层功能抑制对小鼠部分躯体感觉功能的影响，并初步探索可能的环路机制。 方法：采用Tra2b条件性基因敲除建立皮层缺失小鼠模型，化学遗传学方法抑制初级感觉皮层下肢代表区（Primary somatosensory cortex hindlimb region, S1HL）神经元活动；分别采用辐射热、von Frey、轻毛刷和贴纸测试等实验评价对小鼠热痛、机械痛和触觉等躯体感觉的影响。 结果：皮层缺失小鼠辐射热和von Frey刺激反应阈值与对照小鼠相比无显著性差异，但在轻毛刷和贴纸实验中表现出明显的触觉敏化；抑制S1HL脑区明显降低小鼠后爪von Frey刺激反应阈值、提高对非痛性触觉刺激的敏感性，对辐射热痛阈值没有显著影响；束路追踪结果显示S1HL向脑干导水管周围灰质和延髓头端腹外侧部有直接的纤维投射。结论：皮层缺失小鼠触觉敏感性增强；S1HL脑区主要参与小鼠后爪触觉和机械痛觉的下行调控。

Abstract:

Objective: To investigate the effects of cortical deficiency and functional inhibition of primary somatosensory cortex on the behavioral responses to noxious and innocuous stimuli. Methods: Cortexless model was established by Tra2b conditional knockout (cKO), and primary somatosensory cortex hindlimb region (S1HL) was inhibited by chemical genetics manipulation. The Hargreaves and von Frey tests were used to measure the thermal and mechanical pain thresholds, respectively. The brush and adhesive removal tests were used to evaluate tactile sensitivity. Results: Deficiency of cerebral cortex significantly enhanced the mouse tactile sensitivity, but failed to change the thermal and mechanical pain thresholds. Inhibition of S1HL resulted in tactile sensitization and mechanical allodynia of hindpaws. Virus-delivered anterograde tracking showed that both periaqueductal grey (PAG) and rostral ventromedial medulla (RVM) received projections from S1HL. Conclusion: Deficiency of cerebral cortex led to tactile facilitation; S1HL was involved in the descending modulation of tactile sensation and mechanical pain.