摘要
目的研究腹侧被盖区(ventral tegmental area,VTA)多巴胺(dopamine,DA)神经元促肾上腺皮质激素释放激素受体1(corticotropin releasing hormone receptor 1,CRHR1)在焦虑促进实验性咬合干扰(experimental occlusal interference,EOI)致口颌面痛中的作用。方法通过高架十字迷宫实验评估了115只Sprague-Dawley(SD)大鼠焦虑水平,得出SD大鼠焦虑谱并利用K-均值聚类分析建立分型标准。选取高焦虑(high anxiety,HA)和低焦虑(low anxiety,LA)大鼠进行EOI建模,咀嚼肌机械摆头阈值(head withdrawal threshold,HWT)评估EOI后口颌面痛的发展过程(每组7只大鼠);免疫荧光染色检测EOI后6 d VTA DA神经元CRHR1表达量差异(每组6只大鼠)。确认HA大鼠对EOI更敏感后,对HA大鼠进行EOI建模,在体电生理学评估EOI后6 d激活VTA DA神经元CRHR1对神经元放电频率(每组10个神经元,来自5只大鼠)和VTA场电位(每组14个通道,来自5~7只大鼠)的影响;激活VTA DA神经元CRHR1后评估EOI后HWT的变化(每组7只大鼠)。结果SD大鼠的焦虑水平可被分为HA、中焦虑(moderate anxiety,MA)和LA三类(P<0.001)。HA大鼠在EOI后口颌面痛敏发展更快(P<0.01),VTA DA神经元CRHR1表达量更低(P<0.001)。激活VTA DA神经元CRHR1使神经元放电频率显著上升(P<0.05),VTA场电位部分改变(P<0.05),HWT值显著降低(P<0.05)。结论VTA DA神经元CRHR1参与焦虑对EOI致口颌面痛的促进作用。
Objective To investigate the role of the corticotropin releasing hormone receptor 1(CRHR1)of dopamine(DA)neurons of ventral tegmental area(VTA)in experimental occlusion interference(EOI)induced orofacial pain.Methods Anxiety levels of 115 Sprague-Dawley(SD)rats were assessed using the elevated plus maze test to establish an anxiety spectrum,followed by K-means cluster analysis to develop classification criteria.High-anxiety(HA)and low-anxiety(LA)rats were selected for EOI modeling.The development of orofacial pain was evaluated by measuring the mechanical head withdrawal threshold(HWT)in masticatory muscles(7 rats per group).Immunofluorescence staining was performed to examine differences in CRHR1 expression in VTA DA neurons at 6 days post-EOI(6 rats per group).After confirming HA rats'heightened sensitivity to EOI,in vivo electrophysiology was conducted on HA rats to assess the effects of CRHR1 activation in VTA DA neurons on(1)neuronal firing frequency(10 neurons from 5 rats per group),and(2)VTA local field potentials(14 channels from 5-7 rats per group)at 6 days post-EOI.Subsequent HWT measurements were performed following CRHR1 activation in VTA DA neurons(7 rats per group).Results The anxiety levels of SD rats could be classified into three significantly different categories HA,moderate anxiety(MA),and LA(P<0.001).HA rats showed faster development of orofacial pain following EOI(P<0.01),and lower expression of CRHR1 in VTA DA neurons(P<0.001).Activation of CRHR1 in VTA DA neurons significantly increased neuronal firing rates(P<0.05),partially altered the local field potential of VTA region(P<0.05),and significantly decreased HWT values(P<0.05).Conclusions CRHR1 of VTA DA neurons participates in the facilitative effect of anxiety on EOI induced orofacial pain.
作者
张垚君
李源
莫思怡
刘婧雯
徐啸翔
曹烨
Zhang Yaojun;Li Yuan;Mo Siyi;Liu Jingwen;Xu Xiaoxiang;Cao Ye(Department of Prosthodontics,School and Hospital of Stomatology of Peking University,Beijing 100080,China)
出处
《中国医学前沿杂志(电子版)》
北大核心
2025年第7期48-55,共8页
Chinese Journal of the Frontiers of Medical Science(Electronic Version)
基金
国家自然科学基金(82170982)
北京市自然科学基金(7242171,7244443)。
