SEX DIFFERENCES--N REGIONAL U OPIOID RECEPTOR PAIN PROC

性别差异--N 区域 U 阿片受体疼痛过程

• 批准号: 6176686
• 负责人: Jon-Kar Zubieta
• 金额: $ 23.07万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176686
• 关键词: amygdala; analgesia; analgesics; brain imaging /visualization /scanning; clinical research; gender difference; human subject; hypothalamus; magnetic resonance imaging; neurobiology; neurochemistry; opioid receptor; pain; pons; positron emission tomography; prefrontal lobe /cortex; psychophysics; questionnaires; radiotracer; receptor binding; temporomandibular joint syndrome; thalamus

Epidemiological and experimental evidence points to sex differences in the responses to antinociceptive pharmacological agents, the experience of pain, and the prevalence of certain chronic pain conditions, such as temporomandibular disorders (TMD). It has been suggested that these reflect the presence of sex-differences in brain neurochemical systems involved in pain perception and control, and that these may also be hormone-sensitive. The application of functional imaging techniques allows the direct examination of neuronal networks and neurochemical systems involved in the human experience of pain. The overall goal of the proposed research is the description and understanding of relevant aspects of the gender-specific neurobiology that occurs as the human undergoes tonic pain. The current proposal focuses on the opioid system, and specifically the mu opioid receptors, since these sites mediate many of the actions of exogenously administered antinociceptive drugs, as well as stress- and nociception-induced analgesia. Preliminary data using PET demonstrate that regions involved in the modulation of pain, such as the anterior cingulate cortex, prefrontal cortex, amygdala, thalamus and midbrain, show sex-differences in the concentration of mu opioid receptors. Additional findings reveal that the function of these receptors is subject to modulation by circulating estradiol, making this receptor site a logical candidate for the investigation of pain mechanisms and their differences between the sexes. This proposal takes advantage of state-of-the-art brain imaging technology for the quantification of mu opioid receptor sites in the human brain. It combines PET with a validated model of temporomandibular pain to examine the involvement of the mu opioid receptors in the regulation of tonic pain. A randomized, double blind, repeated measures crossover design will be employed to investigate the effect of tonic experimental pain on the opioid function of healthy subjects. The in vivo availability of 4 opioid receptors, as measured in living human subjects with PET and the selective radiotracer [11C]carfentanil will be quantified under baseline, placebo and tonic pain conditions. Baseline regional receptor levels, and receptor occupancy resulting from the administration of control and algesic substances into the masseter muscle, will be quantified. Regional binding and receptor occupancy will be related to psychophysical aspects of pain in men and women. These studies will show for the first time the function of the mu opioid receptor and the endogenous opioid system as the human undergoes pain. It will also examine the effect of sex and the involvement of various brain regions on sensory and affective components of pain.

流行病学和实验证据指出了性别差异 对抗伤害性药理学剂的反应，经验 疼痛和某些慢性疼痛状况的患病率，例如 颞下颌疾病（TMD）。 有人建议这些 反映脑神经化学系统中性别差异的存在 参与疼痛的感知和控制，这些也可能是 激素敏感。 功能成像技术的应用 允许直接检查神经元网络和神经化学 涉及人类疼痛经验的系统。总体目标 拟议的研究是对相关的描述和理解 作为人类的性别特异性神经生物学的方面 经历补品疼痛。当前的建议重点是阿片类药物系统， 特别是MU阿片受体，因为这些位点介导了许多 外源给予的抗伤害感受药的作用 以及压力和伤害感受诱导的镇痛。 初步数据 使用PET证明涉及调节疼痛的区域， 例如前扣带回皮质，前额叶皮层，杏仁核， 丘脑和中脑，在Mu的浓度中显示性别差异 阿片受体。其他发现表明这些功能 受体会通过循环雌二醇进行调节，从而使其 受体部位是研究疼痛的逻辑候选者 机制及其性别之间的差异。 该提议采取了 最先进的大脑成像技术的优势 量化人脑中的MU阿片受体位点。 它 将宠物与经过验证的颞下颌疼痛模型结合起来检查 MU阿片受体参与补品调节 疼痛。 随机，双盲，重复措施交叉设计 将被用来研究补品实验疼痛的影响 关于健康受试者的阿片类药物功能。 体内可用性 在用PET和 选择性radiotracer [11C] Carfentanil将在 基线，安慰剂和补品疼痛状况。 基线区域受体 级别和受体占用率是由 对控制和符号的物质进入咬合肌肉，将是 量化。区域结合和受体占用率将与 男性和女人疼痛的心理物理方面。 这些研究会 首次显示MU阿片受体的功能和 内源性阿片类药物系统会经历疼痛。 它也会 检查性别的影响和各个大脑区域的参与 关于疼痛的感觉和情感成分。