前扣带回BK通道β4亚单位膜转运参与神经病理性痛相关焦虑情绪

The anterior cingulate cortex (ACC) is not only involved in pain perception but also in the modulation of anxiety. And the ACC serves as a critical hub for anxiety-like behavior. However, the molecular and cellular basis of chronic pain-associated anxiety and its interaction with chronic pain is not known. Our previous studies showed an enhanced anxiety-like behavior, which accompanied bilateral mechanical hypersensitivity in the chronic compression of multiple dorsal root ganglia (mCCD) rat. mRNA and protein expression of BK β4 subunits was extremely increased in the ACC after mCCD. Furthermore, fAHP, which mediated by the activation of BK channels was significantly decreased and the excitability was enhanced in ACC neurons in mCCD rats. Local activation of BK channels in the ACC reversed neuropathic pain and anxiety-like behaviors. It is likelyted that the excitability is enhanced due to the decreased function of BK channels in ACC neurons in the neuropathic pain associated anxiety. This change may be one of intrinsic mechanisms in the ACC underlying neuropathic pain associated anxiety. In the present study, with the combination of molecular biological, electrophysiological methods and so on, the cellular and molecular mechanisms underlying electrophysiological characterisitics of BK channel will be explored in the ACC in the neuropathic pain associated anxiety-like behavior. The novel mechanism that AC1 modulates membrane trafficking of BK β4 subunits may be further elucidated in the ACC in chronic pain associated anxiety-like behavior. The new role and modulatory mechanisms of the enhanced excitatory synaptic transmission will be in the insular cortex in the chronicity of pain. The proposed study may lay an important theoretical and experimental basis for illuminating cortical mechanisms of in chronic pain associated anxiety.

前扣带回（ACC）既参与痛觉又能调控焦虑样情绪，是参与焦虑样行为的中心环节之一，但是慢性痛引起焦虑的分子和细胞学机制目前尚不清楚。我们前期工作观察在神经理性痛伴随焦虑样行为的时间点上，ACC BK通道β4亚单位mRNA和蛋白表达明显上调， BK通道介导ACC神经元的快速后超级化电位明显减小，神经元兴奋性增加，ACC定位注射BK通道激动剂可以翻转多节段背根节慢性压迫大鼠的机械性痛和焦虑样行为。我们首次提出ACC BK通道功能降低，引起神经元兴奋性增加，可能是ACC参与神经病理性痛焦虑样行为的内在机制之一。本项目拟采用分子生物学、脑薄片全细胞记录等手段，阐明ACC BK通道在神经病理性痛相关焦虑样行为中电生理学特征变化的细胞学和分子机制，以及AC1调控BK通道β4亚单位膜转运的新机制。为揭示ACC参与慢性痛相关焦虑情绪信息加工和处理的活动规律，阐明慢性痛焦虑的皮层机制提供重要理论和实验依据。

前扣带回(ACC)既参与痛觉又能调控焦虑样情绪,是参与焦虑样行为的中心环节之 一,但是慢性痛引起焦虑的分子和细胞学机制目前尚不清楚。我们前期工作观察在神经理 性痛伴随焦虑样行为的时间点上,ACCBK通道β4亚单位mRNA和蛋白表达明显上调,BK通道介导ACC神经元的快速后超级化电位明显减小,神经元兴奋性增加,ACC定位注射BK通道激动剂可以翻转多节段背根节慢性压迫大鼠的机械性痛和焦虑样行为。我们首次提出ACCBK通道功能降低,引起神经元兴奋性增加,可能是ACC参与神经病理性痛焦虑样行为的内在机制之一。本项目拟采用分子生物学、脑薄片全细胞记录等手段,阐明ACCBK通道在神 经病理性痛相关焦虑样行为中电生理学特征变化的细胞学和分子机制,以及AC1调控BK通道β4亚单位膜转运的新机制。为揭示ACC参与慢性痛相关焦虑情绪信息加工和处理的活动 规律,阐明慢性痛焦虑的皮层机制提供重要理论和实验依据。

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