HU210缓解慢性神经病理性疼痛诱发的焦虑抑郁样行为机制研究

The mechanism of HU210 attenuates anxiety and depression-like behavior induced by chronic neuropathic pain

摘要:

目的：探讨外源性大麻素HU210在小鼠神经病理性疼痛诱发的焦虑、抑郁样行为中的作用，以及对腹外侧眶皮层 (ventrolateral orbital cortex, VLO) 锥体神经元自发电活动的影响。方法：利用腓总神经 (common peroneal nerve, CPN) 结扎建立神经病理性疼痛模型，采用Von Frey纤毛检测小鼠的触诱发痛，利用高架十字迷宫、强迫游泳等行为学实验来评估小鼠的焦虑和抑郁样行为；利用在体细胞外记录方法记录VLO中锥体神经元自发放电活动的变化。结果：CPN结扎小鼠在术后第7天的50%缩足阈值 (50% Paw withdrawal threshold, 50% PWT) 显著降低，并持续至术后第35天；CPN结扎后第13天，小鼠在高架十字迷宫中进入开臂次数百分比和开臂时间百分比显著减少，在强迫游泳测试中不动时间显著增加；CPN结扎后第13天，腹腔注射20 μg/kg HU210或VLO定位注射200 ng HU210都能够显著增加小鼠在高架十字迷宫中进入开臂次数百分比和开臂时间百分比，并显著减少强迫游泳测试中的不动时间；CPN结扎后第13天，小鼠VLO中锥体神经元自发放电频率显著降低，腹腔注射20 μg/kg HU210能够显著增加锥体神经元的自发放电频率。结论：外源性大麻素HU210可能通过增加VLO中锥体神经元的自发放电频率缓解神经病理性疼痛引起的焦虑和抑郁样行为。

Abstract:

Objective: To investigate the role of exogenous cannabinoid HU210 in anxiety and depression-like behaviors induced by chronic neuropathic pain in mice and the effects on spontaneous firing of ventrolateral orbital (VLO) pyramidal neurons. Methods: A neuropathic pain model was established by ligation of common peroneal nerve (CPN) and allodynia was measured with Von Frey filaments. Anxiety- and depression-like behaviors were assessed by elevated plus maze and forced swimming test. The change of the spontaneous firing of pyramidal neurons in VLO was observed by extracellular recording in vivo. Results: CPN ligation mice showed a significant reduction of 50% paw withdrawal threshold (50% PWT) from day 7 to day 35. On the 13th day after CPN ligation, mice in the CPN group spent significantly less time and frequency in the open arms in the elevated plus maze and more immobility time in the forced swimming test. Intraperitoneal injection of 20 μg/kg HU210 or microinjection of 200 ng HU210 in the VLO on the 13th day after CPN ligation, mice spent significantly more time and frequency in the open arms in the elevated plus maze and less immobility time in the forced swimming test. The spontaneous firing rate of VLO pyramidal neurons reduced significantly after CPN ligation on day 13, which could be increased by intraperitoneal injection of 20 μg/kg HU210. Conclusion: Exogenous cannabinoid HU210 attenuates anxiety and depression-like behaviors induced by chronic neuropathic pain in mice, which may be related to the alternation of spontaneous firing rate of pyramidal neurons in VLO.