蓝斑核参与抑郁导致的慢性疼痛行为的调控  

Involvement of locus coeruleus in the regulation of depression-induced chronic pain behavior

作　　者：袁溪 刘雨晴 孟浅 Yuan Xi;Liu Yuqing;Meng Qian(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine of Ministry of Education,Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Hefei 230032)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,抗炎免疫药物安徽省协同创新中心,合肥230032

出　　处：《安徽医科大学学报》2024年第9期1517-1524,共8页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82101311);安徽医科大学校科研基金项目(编号:2020xkj014);安徽医科大学临床医学(“5+3”一体化)专业“早期接触科研”训练计划(编号:2021-ZQKY-172)。

摘　　要：目的探究蓝斑核(LC)是否参与介导小鼠抑郁伴疼痛行为及可能机制。方法雄性C57BL/6J小鼠随机分为对照组和慢性束缚应激(CRS)组,通过新奇抑制进食、悬尾和强迫游泳等行为学实验检测抑郁样行为的形成,评估小鼠CRS模型的建立;使用Von Frey毛刷检测小鼠的机械痛阈;通过c-Fos免疫荧光染色确定LC神经元活性在抑郁伴疼痛小鼠中的改变;利用离体脑片电生理检测LC神经元兴奋性变化;通过化学遗传学技术调控LC活性,观察小鼠的疼痛及抑郁样行为表现。结果与对照组相比,CRS小鼠在束缚第3周(CRS 3W)出现明显的抑郁样行为,模型建立成功;CRS 3W小鼠机械痛阈显著下降,出现机械痛敏;CRS 3W小鼠LC区有大量c-Fos+表达,且90%为去甲肾上腺素(NE)能神经元;CRS 3W小鼠LC中NE能神经元兴奋性降低。而且,化学遗传学激活LC可显著缓解CRS 3W小鼠的机械痛敏。结论CRS 3W小鼠LC中NE能神经元兴奋性下降,化学遗传学激活LC中NE能神经元可缓解CRS 3W小鼠的机械痛敏。Objective To explore whether the locus coeruleus(LC)mediates the pain in mice with depressive-like behaviors and underlying mechanisms.Methods Male C57BL/6J mice were randomly divided into two groups,including control and chronic restraint stress(CRS)group.Novelty-suppressed feeding test,tail suspension test and forced swimming test were used to assess the formation of depressive-like behaviors and the establishment of CRS model.The mechanical pain threshold of mice was detected by Von Frey brush test.LC neuronal activity was detected by c-Fos immunofluorescence staining.Neuronal excitability in LC was detected using electrophysiology of isolated brain slices.The influence on pain and depressive-like behaviors was identified by chemogenetics in LC.Results Compared with the Control group,CRS mice displayed significant depressive-like behavior after 3 weeks of CRS(CRS 3W),and the model was successful;CRS 3W mice showed a significant decrease in mechanical pain threshold and developed mechanical pain sensitivity.A lot of c-Fos+cells of LC was observed in CRS 3W mice,90%of them were noradrenergic neurons.Compared with the Control group,the neuronal excitability of noradrenergic neurons decreased in LC of CRS 3W mice.Compared with the Control group,chemogenetic activation of the LC noradrenergic neurons significantly reduced mechanical pain sensitization in CRS 3W mice.Conclusion The excitability of noradrenergic neurons in LC of CRS 3W mice decreases,and chemogenetic activation of noradrenergic neurons in LC can relieve pain sensitization in CRS 3W mice.

关 键 词：蓝斑核 化学遗传学 慢性疼痛 慢性束缚应激 电生理 新奇抑制进食 强迫游泳 

分 类 号：R749.42[医药卫生—神经病学与精神病学] R749.06[医药卫生—临床医学]