疼痛敏感性的性别差异:负性情绪的作用及其脑机制
文献类型：学位论文
| 作者 | 张会娟 |
| 答辩日期 | 2021-12 |
| 文献子类 | 博士 |
| 授予单位 | 中国科学院心理研究所 |
| 授予地点 | 中国科学院心理研究所 |
| 其他责任者 | 胡理 |
| 关键词 | 能疼痛敏感性 性别差异 负性情绪 脑结构 脑功 |
| 学位名称 | 理学博士 |
| 学位专业 | 认知神经科学 |
| 其他题名 | Sex differences in pain sensitivity:the role of negative emotions and its neural mechanisms |
| 中文摘要 | Pain sensitivity varies widely among individuals. Among the factors influencing individual differences in pain sensitivity, sex differences play an important role. Notably, sex differences in pain sensitivity have been consistently demonstrated in experimental and clinical investigations, that is, females usually report a higher pain sensitivity in response to noxious stimuli of different modalities than males. Previous studies reported that females typically experience more negative emotions during pain processing, especially fear, anxiety, and depression, and these differences could represent plausible contributors to sex differences in pain sensitivity. However, the specific role of negative emotions in sex differences in pain sensitivity remains unclear, the factors influencing sex differences in pain threshold and pain tolerance remains inconclusive, and the neural mechanism underlying sex differences in pain sensitivity needs to be explored. To address the above issues, 450 healthy individuals(160 men and 290 women) were recruited in the present study, pain sensitivity (i.e., pain threshold and tolerance)，negative emotions (i.e.，pain-related fear, pain-related anxiety, trait anxiety, and depression), and MRI data (i.e., high-resolution T1 structural images and resting一state functional images) were collected by using psychophysical methods and magnetic resonance brain imaging technology. Firstly, to explore the sex differences in pain sensitivity and the role of negative emotion variables (i.e.，fear of pain, pain-related anxiety, trait anxiety, and depression) in different pain sensitivity indexes (pain threshold and pain tolerance), we quantified negative emotions using well一established questionnaires and pain sensitivity using the cold pressure test, and assessed the mediation relationship among sex, negative emotions and pain sensitivity using structural equation modeling in Study 1 .The results showed that, compared with males, females had a lower pain threshold and pain tolerance in response to cold pain, and reported higher scores in pain-related negative emotions (fear and anxiety). In addition, pain-related negative emotions were negatively correlated with pain threshold/tolerance for all subjects. While correlations between the pain-related fear and pain threshold/tolerance in males were significantly higher than that in females, and no significant differences in the correlation trend between pain-related anxiety and pain threshold/tolerance were found between males and females. At last, mediation analysis results showed that pain-related fear and anxiety were complementary mediators of the relationship between sex and pain threshold, and they were indirect-only mediators of the relationship between sex and pain tolerance. The results indicated that sex differences in pain sensitivity were mediated by pain-related fear and anxiety and the pain threshold and pain tolerance differ considerably in their loading on physiological and psychological components. Specifically, pain threshold could be influenced not only by physiological components (i.e.，sex) but also by psychological components，while pain tolerance may load more psychological components. Secondly, to explore the brain structural underpinnings of sex difference in pain sensitivity, we collected high-resolution T1 structural images and performed cortical thickness and subcortical volume analyses in Study 2. The theoretical model was built to quantify the mediation relationship among sex, negative emotions, structural brain features, and pain sensitivity using path analyses and structural equation modeling. The results showed that the amygdala volume was significantly larger in males than that in females, and pain-related fear was negatively correlated with the volumes of the amygdala in the left hemisphere, especially the subnuclei of the lateral nucleus, basal nucleus, accessory basal nucleus, and cortico一amygdaloid transition area. Results of mediation analysis showed that the amygdala subnuclei (i.e., the lateral and basal nuclei in the left hemisphere) volumes were the complementary mediators on the relationship between sex and pain-related fear. The final structural equation model revealed the specific relationship among sex, pain-related negative emotions, amygdala volumes, and pain sensitivity, suggesting that the amygdala subnuclei volumes subserved the neural underpinnings of sex differences in pain sensitivity through the modulation of pain-related fear. Lastly, to explore the resting-state brain functional features of sex differences in pain sensitivity, we collected resting-state functional data and performed amplitude of low-frequency fluctuations analysis and regions of interest (ROIs)-based and seed-based resting-state functional connectivity analyses in Study 3 and Study 4, respectively. Although significant sex differences in regional brain activities were detected in Study 3, no correlations were found between regional brain activities and pain sensitivity or negative emotions. In Study 4, results of the ROIs-based functional connectivity revealed that the strength of the functional connectivity between the cerebellum and frontal pole/occipital pole in males was significantly higher than that in females, and this circuit functional connectivity was significantly correlated with pain sensitivity. Moreover, the functional connectivity between the cerebellum and frontal pole/occipital pole mediated the relationship between sex and pain threshold and then influenced pain tolerance. Results of seed-based (i.e., the amygdala and subregions) functional connectivity showed that the correlations between amygdala functional connectivity and pain sensitivity/pain-related negative emotions were significantly different between males and females. These results demonstrated that the amygdala and its subregions might have sex-specific effects in the correlation with pain threshold and pain-related negative emotions. In summary, this study systematically investigated the role of negative emotions in sex differences in pain sensitivity and its underlying neural mechanisms based on a large sample of behavioral, brain structural, and resting-state functional data. This study provides new insights into the neuropsychological underpinnings of sex differences in pain sensitivity and emphasizes the important role of pain-related negative emotions and the amygdala in this process. It should be noted that the sex and negative emotion levels should be considered in the evaluation, diagnosis, and treatment for clinical pain, which is important to tailor a personalized method for treating pain according to the sex and the level of pain-related negative emotions for patients with painful conditions. |
| 英文摘要 | 疼痛敏感性存在较大的个体差异，在众多影响疼痛敏感性个体差异的因素中，性别这一因素不容忽视。实验室和临床研究均己证实疼痛敏感性在性别间存在差异，即女性较男性对多种模态的伤害性刺激诱发的疼痛有更高的敏感性。尽管先前研究表明在疼痛加工过程中不同性别群体所体验到的状态性的负性情绪水平存在差异，尤其是恐惧、焦虑和抑郁，这些差异可能在疼痛敏感性性别差异中起着重要作用。但口前对于特质性的负性情绪在疼痛敏感性性别差异中的具体作用方式仍不清楚;不同疼痛敏感性指标间性别差异的影响因素是否一致仍没有定论; 是否存在大脑结构和功能上的特征可以揭示疼痛敏感性性别差异的神经机制还有待进一步探究。因此，本研究以450名健康被试(160名男性和290名女性)为研究对象，通过心理物理学方法和磁共振脑成像技术采集包含行为学、脑结构和静息态脑功能影像的大样本数据，以系统研究负性情绪在疼痛敏感性性别差异中的作用及其脑机制。 首先，为探究疼痛敏感性(疼痛闽限和耐受闽限)在性别间的差异及负性情绪(包括疼痛恐惧、疼痛相关焦虑、特质焦虑和抑郁)在疼痛敏感性性别差异中的作用，研究一通过问卷测量和冷压痛测试分别采集被试的负性情绪评分和疼痛敏感性指标，并对性别、负性情绪和疼痛敏感性之间的关系进行中介分析。分析结果显示:女性的疼痛敏感性及与疼痛相关的负性情绪评分(疼痛恐惧和疼痛相关焦虑)显著高于男性。此外，所有被试的疼痛恐惧和疼痛相关焦虑评分与其疼痛闽限和耐受闽限呈负相关。其中，男性的疼痛恐惧水平与疼痛闽限和耐受闽限的相关程度要显著高于女性，而两组被试在疼痛焦虑水平与疼痛闽限和耐受闽限的相关程度上无显著差异。最后，中介分析结果显示，疼痛恐惧和疼痛相关焦虑在性别和疼痛闽限之间的关系中起连续补充性的中介作用，而在性别与疼痛耐受闽限的关系中起连续的间接的中介作用。以上研究结果表明疼痛恐惧和疼痛相关焦虑介导了疼痛敏感性的性别差异，且它们对疼痛闽限和耐受闽限性别差异的作用模式不完全相同，提示与疼痛闽限直接受性别影响相比，疼痛耐受闽限可能负载更多的心理成分。 其次，为探究疼痛敏感性性别差异的脑结构基础，研究二采集被试的T1结构像数据并提取其脑结构指标(皮层厚度和皮层下结构体积)，通过中介分析和结构方程模型构建性别、脑结构特征、疼痛相关负性情绪和疼痛敏感性之间的关系。结果显示:男性的杏仁核体积显著大于女性;疼痛恐惧与左侧杏仁核的灰质体积，特别是其亚核中的外侧核、基底核、副基底核以及皮质一杏仁核过渡区的体积，呈显著负相关;中介分析结果显示，左侧杏仁核的外侧核和基底核体积在性别和疼痛恐惧之间起互补性中介作用。最终的结构方程模型进一步揭示了杏仁核的外侧核和基底核体积可以通过调节疼痛恐惧的性别差异进而影响疼痛相关焦虑，最终对痛敏感性的性别差异产生影响。 最后，为探究疼痛敏感性性别差异的脑功能基础，研究三和研究四通过采集被试的静息态功能磁共振数据，分别从局部脑功能和脑回路一脑网络层面进行了低频振荡振幅和静息态功能连接分析。研究三发现了在局部脑功能上存在性别差异的脑区，但未发现与疼痛敏感性或负性情绪相关的局部脑功能特征。研究四从全脑功能网络层面揭示了男性在小脑与额极和枕极之间的功能连接强度显著高于女性，此功能连接强度与疼痛敏感性显著相关，且可以通过中介性别和疼痛闽限之间的关系，进而对疼痛耐受闽限产生影响。其次，以杏仁核为种子点进行的脑回路功能连接分析显示，男女两组被试在杏仁核功能连接与疼痛敏感性或疼痛相关负性情绪的相关在方向上存在显著的差异，该结果提示杏仁核及其亚区的功能连接模式与疼痛敏感性及疼痛相关负性情绪的关联可能在性别间存在一定的特异性。 综上所述，本研究基于大样本的行为学、脑结构和静息态脑功能磁共振数据，系统考察了负性情绪在疼痛敏感性性别差异中的作用及其脑结构和功能基础。本研究为疼痛敏感性性别差异的心理和脑机制提供了新的见解，强调了疼痛相关负性情绪及杏仁核在其中的重要作用。本研究提示我们在临床疼痛的评估、诊断和治疗过程中，应考虑性别和负性情绪水平对患者疼痛的影响，根据患者的性别和负性情绪水平进行个体化的治疗可能会对患者疼痛的缓解具有积极意义。 |
| 语种 | 中文 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/41340]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 推荐引用方式 GB/T 7714 | 张会娟. 疼痛敏感性的性别差异:负性情绪的作用及其脑机制[D]. 中国科学院心理研究所. 中国科学院心理研究所. 2021. |
入库方式： OAI收割
来源：心理研究所
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