Brain Mechanisms Supporting Individual Differences in Pain

描述（由申请人提供）：急性和慢性疼痛都与人类痛苦的不可估量的代价有关，并提出了一个重大的经济问题。治疗疼痛的主要挑战之一来自疼痛的主观报告中的巨大个体间差异。有类似伤害的人经常会报告非常痛苦的经历。由于担心疼痛主观报告的有效性或准确性，这种个体差异往往导致治疗不足。尽管疼痛的个体差异具有深刻的临床意义，但人们对支持这种差异的基本大脑机制知之甚少。这种个体间主观差异的一部分 疼痛的报告可能是由于身体因素，如大脑连接。其他成分来自心理倾向，可能涉及认知控制、冲动、抑郁和焦虑等因素。最后，人口统计学变量，如性别和种族也可能大大有助于疼痛敏感性的个体差异。令人惊讶的是，我们对这些因素影响单个个体疼痛体验的大脑机制知之甚少。因此，拟议研究的基本目的是描绘引起疼痛敏感性个体差异的大脑机制。我们将从大量（392）志愿者中获取功能和结构MRI数据。招募的目的是获得一个真正的社区样本，以促进调查结果的普遍性。因此，这项研究将涉及不同社会经济水平的个人，肥胖的个人，患有积极抑郁和焦虑的个人，以及那些身体和精神健康状况良好的人。参与者还将接受广泛的感官测试和心理评估，以充分表征他们的疼痛表型。将使用多元回归统计分析来识别与结构和功能神经成像数据中灵敏度的个体间差异相关的脑区域。技术，如心理生理学的相互作用分析将被用来测试有关疼痛敏感性的功能连接的影响的假设。大脑机制的识别， 疼痛敏感性的个体差异将大大有助于我们对疼痛的大脑机制的基本理解，并将批判性地评估我们现有的观念，即每个人都以相同的方式处理伤害性信息。拟议研究的结果将为制定个性化疼痛治疗策略提供坚实的理论基础。

DESCRIPTION (provided by applicant): Both acute and chronic pain are associated with an incalculable toll in human suffering and present a significant economic problem. One of the major challenges in treating pain arises from the tremendous inter- individual variation in subjective reports of pain. Individuals with similar injuries will frequently report vastly differet experiences of pain. Such individual differences often result in inadequate treatment due to concerns about the validity or veracity of subjective reports of pain. Despite the profound clinica significance of individual differences in pain, remarkably little is known about the basic brain mechanisms that support such differences. Portions of this inter-individual variation in subjective reports of pain may be due to physical factors such as brain connectivity. Other components arise from psychological disposition and may involve factors such as cognitive control, impulsivity, depression, and anxiety. Finally, demographic variables such as sex and ethnicity may also substantially contribute to individual differences in pain sensitivity. Surprisingly littl is known about the brain mechanisms by which these factors influence the construction of the pain experience at the level of a single individual. Thus, the fundamental aim of the proposed research is to delineate the brain mechanisms that give rise to individual differences in pain sensitivity. We will acquire both functional and structural MRI data from a large number (392) of volunteers. Recruitment will be designed to obtain a true community sample in order to facilitate generalizability of findings. As such, this research will involve individuals of differing socio-economic levels, obese individuals, individuals with active depression and anxiety, as well as those in excellent physical and mental health. Participants will also undergo extensive sensory testing and psychological evaluation in order to fully characterize their pain phenotype. Multiple regression statistical analyses will be used to identify brain regions related to inter-individual differences in sensitivity in both structural and functional neuroimaging data. Techniques such as psychophysiological interaction analyses will be used to test hypotheses about the influence of functional connectivity on pain sensitivity. The identification of brain mechanisms that support individual differences in pain sensitivity will contribute substantially to our basic understandingof brain mechanisms of pain and will critically evaluate our existing notions that every individual processes nociceptive information in the same way. The results from the proposed studies will provide a solid rationale for the development of individualized pain treatment strategies.