FIBROMYALGIA--CENTRAL FACTORS IN ITS ETIOPATHOGENESIS

这项研究的目的是为了更好地了解核心因素， 参与改变疼痛感知的发病机制， 纤维肌痛（FM）。我们将测试从一个模型中得出的六个假设， 假定神经内分泌和免疫异常，其特征在于 脑脊液（CSF）5-羟色胺减少，CSF P物质（SP）可引起中枢神经系统致敏 参与疼痛感知的结构，即，丘脑和尾状核 原子核局部脑血流量（rCBF）减少， 结构作为这种敏化过程的标记， 与全身性低痛阈和其他改变有关， 疼痛感知，独立于精神疾病的影响，或 心理状态该模型还假定，升高的CSF SP可能在 部分是由于CSF白细胞产生SP信使（m）RNA。我们 建议测量（1）皮质、丘脑和尾状核的rCBF，（2） 5-羟色胺代谢物5-羟基吲哚乙酸（5-HIAA）的CSF水平， SP、CSF白细胞数、白细胞SP mRNA水平;（3）痛阈 感觉辨别能力和反应偏差的指标， 压痛点和控制点对测痛仪刺激的反应，以及（4） 心理状态和终身精神病诊断的数量。这些 将使用（l）80例美国FM患者评估变量 流变学学院（ACR）标准来自流变学诊所 在UAB和库珀绿色医院（“患者”），（2）50名社区居民 年龄、性别、教育程度和种族相似的肌肉骨骼疼痛患者 符合FM的ACR标准，但未寻求医疗护理的人 他们的症状在过去10年（“非患者”），和（3）50个社区 具有可比人口统计学特征且无肌肉骨骼疼痛的居民 不符合FM ACR标准的患者（“对照品”）。使用非- 在精神病发病率方面与对照组无差异的患者， 使我们能够确定丘脑的rCBF水平是否改变， 尾状核与痛觉和神经化学有关 无论受试者的精神病史如何。这项研究 首先检查rCBF与中央结构之间的关系， 参与疼痛感知的神经递质和受试者对 有害刺激，同时控制心理变量。结果 这项研究将促进我们对这些角色的认识， 中枢神经系统和神经内分泌及免疫异常 参与改变患者和社区居民的疼痛感知 关于FM此外，该项目的结果可能会导致发展 药物干预将使rCBF正常化， 结构，从而减少FM患者的疼痛。

The aim of the proposed study is to better understand the central factors involved in the etiopathogenesis of altered pain perception in fibromyalgia (FM). We will test six hypotheses drawn from a model which posits that neuroendocrine and immunologic abnormalities, characterized by decreases in cerebrospinal fluid (CSF) serotonin and increases in CSF substance P (SP), lead to sensitization of central nervous system structures involved in pain perception, i.e., thalamus and caudate nucleus. Decreases in regional cerebral blood flow (rCBF) to these structures serve as markers for this sensitization process and are associated with generalized low pain thresholds and other alterations in pain perception, independently of the effects of psychiatric morbidity or psychological status. The model also posits that elevated CSF SP may in part be due to SP messenger (m) RNA production by CSF leukocytes. We propose to measure (l) rCBF to cortex, thalamus, and caudate nucleus, (2) CSF levels of serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), SP, CSF leukocyte number, and leukocyte SP mRNA level, (3) pain thresholds and indices of sensory discrimination ability and response bias in response to dolorimeter stimulation of tender and control points, and (4) psychological status and number of lifetime psychiatric diagnoses. These variables will be assessed using (l) 80 patients with FM by American College of Rheumatology (ACR) criteria drawn from the Rheumatology clinics at UAB and Cooper Green Hospital ("Patients"), (2) 50 community residents of comparable age, gender, education, and race with musculoskeletal pain who fulfill ACR criteria for FM, but who have not sought medical care for their symptoms in the past 10 years ("Non-Patients"), and (3) 50 community residents of comparable demographic features without musculoskeletal pain who do not fulfill ACR criteria for FM ("Controls"). The use of non- patients, who do not differ from controls in psychiatric morbidity, will allow us to determine if altered levels of rCBF to the thalamus and caudate nucleus are associated with pain perception and neurochemical levels regardless of subjects' psychiatric histories. This study is the first to examine relationships among rCBF to central structures and neurotransmitters involved in pain perception and subjects' responses to noxious stimuli while controlling for psychological variables. The results of this study will advance our knowledge regarding the roles of the central nervous system and neuroendocrine and immunologic abnormalities involved in altered pain perception among patients and community residents with FM. In addition, the results of the project may lead to development of pharmacologic interventions that will normalize rCBF to central brain structures and thus decrease pain among patients with FM.