PSYCH OpenIR  > 健康与遗传心理学研究室
安慰剂镇痛效应反应与不反应现象机制研究
Project Number31371038
郭建友
Subtype面上项目
Project Source国家自然科学基金
Project Level国家级项目
2014
End Date2017-12-31
Abstract安慰剂镇痛效应在常规临床实践中有着非常重要的作用和意义,但受试人群可以分为安慰剂反应者和不反应者。由于人类实验研究的伦理学限制,安慰剂镇痛效应反应和不反应现象的机制至今不明。我们前期的研究表明,动物安慰剂镇痛效应同样存在个体差异。本项目利用建立的安慰剂动物模型,测定大鼠前额叶皮层(PFC)和伏隔核(NAc)多巴胺(DA)含量,确定脑内DA水平与安慰剂镇痛效应强弱相关性;测定PFC、NAc儿茶酚氧位甲基转移酶(COMT)基因启动子区甲基化程度,阐明导致脑内DA水平不同的机制;PFC、NAc单次或多次给予COMT抑制剂或DA受体激动剂,测定前蝝扣带皮层μ阿片受体和PFC胆囊收缩素(CCK)受体变化,明确DA对μ阿片受体和CCK受体表达的影响,揭示DA间接参与安慰剂镇痛效应的途径。该研究将有助于揭示安慰剂镇痛效应强弱的中枢机制,并可能为加强安慰剂镇痛效应提供理论依据,具有重要的理论和实际意义。
Other AbstractThe placebo analgesia response plays an important role in clinical practice, however, participants can be divided into placebo analgesia responder and non-responder. In a recent research, we found that there are also individual difference in placebo analgesia in animal research. In the present study, we use the previously animal model to study the mechanism uderlying placebo analgesia responder and non-responder. The dopamine level in prefrontal cortex (PFC) and nucleus accumbens (NAc) was measured to correlate with the placebo analgesia response. The methylation of catechol-O-methyltransferase (COMT) promoter in PFC and NAc was observed to determine the mechanism uderlying individual differences in DA concentration. Then, the μ opioid receptor in rostral anterior cingulate cortex (rACC) and cholecystokinin (CCK) receptor level in PFC were measured after the COMT inhibitor or the dopamine agonist was microinjected once or multiple times, which can reveal the mechanism of DA level on individual differences in placebo analgesia. In conclusion, this research will help to understand the mechanism underlying placebo responder and non-responder. Furthermore, this study will improve our ability to use of placebo analgesia in clinic. Therefore, the present experiment has important theoretical and practical value.
Project Funding73
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Project Intro.安慰剂镇痛效应在常规临床实践中有着非常重要的作用和意义,但受试人群可以分为安慰剂反应者和不反应者。由于人类实验研究的伦理学限制,安慰剂镇痛效应反应和不反应现象的机制至今不明。我们前期的研究表明,动物安慰剂镇痛效应同样存在个体差异。本项目利用建立的安慰剂动物模型,测定大鼠前额叶皮层(PFC)和伏隔核(NAc)脑区基础多巴胺(DA)及给予预期信号后DA释放水平,确定PFC脑区的基础DA水平影响产生安慰剂镇痛效应,NAc脑区的DA水平则与安慰剂镇痛效应无关。通过测定PFC脑区儿茶酚氧位甲基转移酶(COMT)酶活性、COMT蛋白及mRNA表达水平,阐明PFC脑区多巴胺(DA)水平与该脑区的COMT酶活性直接相关;通过测定PFC脑区COMT基因启动子区甲基化水平,确定该脑区OMT基因启动子区甲基化水平决定COMT酶活性及蛋白水平,进而影响该脑区的DA水平。测定脑内前扣带皮层嘴侧(rACC)的μ阿片受体表达水平和前额皮层(PFC)的胆囊收缩素B(CCK-B)受体表达水平,确定rACC脑区μ阿片受体和PFC脑区的CCK-B受体水平是产生安慰剂镇痛效应强弱的直接原因,rACC脑区的较高表达的μ阿片受体和PFC脑区的低表达的CCK-B受体水平可产生较强的安慰剂镇痛效应。通过给脑内单次或多次微量注射儿茶酚氧位甲基转移酶(COMT)抑制剂和多巴胺(DA)受体激动剂,测定其μ阿片受体和CCK-B受体的影响,进一步确定rACC脑区的μ阿片受体和PFC脑区的CCK-B受体水平是产生安慰剂镇痛效应的,PFC脑区的DA水平并不是产生安慰剂镇痛效应强弱的直接原因。该研究将有助于揭示安慰剂镇痛效应强弱的中枢机制,并可能为加强安慰剂镇痛效应提供理论依据,具有重要的理论和实际意义。
Document Type项目
Identifierhttp://ir.psych.ac.cn/handle/311026/31143
Collection健康与遗传心理学研究室
Affiliation中国科学院心理研究所
First Author AffilicationInstitute of Psychology, Chinese Academy of Sciences
Recommended Citation
GB/T 7714
郭建友.安慰剂镇痛效应反应与不反应现象机制研究.2014.
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