蓝斑介导右美的镇痛镇静作用的神经机制研究  

The mechanisms of locus coeruleus mediates the analgesic and sedative effects of dexmedetomidine

作　　者：施伍 贾欣 梁悦 胡丹丹 王烈成 张玲 Shi Wu;Jia Xin;Liang Yue(Biopharmaceutical Research Institute,Anhui Medical University,Hefei 230032;The First Affiliated Rehabilitation Hospital of Tongji University Medical College,Shanghai 200090;Dept of Anatomy,Embryology and Neurobiology,School of Medicine,Tongji University,Shanghai 200092)

机构地区：[1]安徽医科大学基础医学院生理学教研室,合肥200032 [2]同济大学医学院附属第一康复医院,上海200090 [3]同济大学医学院解剖、组胚与神经生物系,上海200092

出　　处：《安徽医科大学学报》2020年第6期831-836,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:31271182、31571086、81571293)。

摘　　要：目的研究右美托咪定(DEX)对脑干蓝斑(LC)神经元兴奋性的作用以期阐明DEX镇痛和镇静作用的中枢机制。方法以行为学和药理学的方法检测DEX对成年雄性C57BL/6小鼠的机械痛、热痛阈值的影响,并对小鼠进行镇静的行为评分;以在体多通道电生理学技术检测DEX对自由活动的小鼠LC神经元放电的影响;通过行为学方法检测鞘内注射α2受体拮抗剂和吗啡受体拮抗剂对DEX镇痛及镇静作用的影响。结果腹腔注射高剂量DEX(12~20μg/kg)时,小鼠的机械痛和热痛阈值明显增高,且表现出明显的镇静,并且DEX的镇静和镇痛作用均有剂量依赖性;在体多通道电生理记录实验显示腹腔注射低剂量DEX增加LC神经元的放电频率,而高剂量DEX则抑制LC神经元的放电频率;鞘内注射α2受体拮抗剂育亨宾显著抑制低剂量DEX的镇痛作用,却不影响高剂量DEX引起的镇静作用;鞘内注射吗啡受体拮抗剂纳洛酮不影响DEX的镇痛作用。结论 DEX通过激活蓝斑的下行抑制系统发挥镇痛作用,并且DEX镇痛作用由脊髓α2受体介导,而DEX的镇静作用则不通过蓝斑到脊髓的下行抑制系统起作用。Objective To study the effects of dexmedetomidine(DEX)on the excitability of locus coeruleus(LC)neurons in the brain stem in order to elucidate the central mechanisms of the analgesic effects of DEX.Methods The effects of DEX on the mechanical and thermal pain thresholds in adult male C57 BL/6 mice were examined and the sedative behavior scores were evaluated.The effects of DEX on the discharge of LC neurons in free moving mice were measured by multichannel electrophysiology in vivo.The analgesic and sedative effects of DEX were detected by behavioral tests with intrathecal injection ofα2 receptor antagonists or morphine receptor antagonists.Results Dex in high dose(12~20μg/kg)intraperitoneal injected could increase the thresholds of mechanical and thermal pain in mice and they showed significant sedation.Both the sedative and analgesic effects of DEX were dose-dependent.Multichannel electrophysiological recordings in vivo showed that the discharge frequencies of LC neurons were increased by DEX in low dose,while they were decreased by DEX in high dose.Intrathecal injection of yohimbine,anα2 receptor antagonist,significantly inhibited the analgesic effect of DEX in low dose,but did not affect the sedative effect of DEX in high dose.Intrathecal injection of naloxone,a morphine receptor antagonist,did not affect the analgesic effect of DEX.Conclusion DEX exerts analgesic effects by activating the descending inhibition system of LC,and the spinalα2 receptor involves in analgesic effects of DEX.Nevertheless,the sedative effects of DEX are not mediated by the descending inhibition system from LC to spinal cord.

关 键 词：右美托咪定 纳洛酮 育亨宾 蓝斑 

分 类 号：Q423[生物学—神经生物学] Q424[生物学—生理学]