FIBROMYALGIA--CENTRAL FACTORS IN ITS ETIOPATHOGENESIS

本研究的目的是更好地了解纤维肌痛（FM）疼痛感知改变的发病机制所涉及的核心因素。我们将测试从一个模型中得出的六个假设，该模型假定神经内分泌和免疫异常，其特征在于脑脊液（CSF）5-羟色胺减少和SCF P物质（SP）增加，导致涉及疼痛感知的中枢神经系统结构的敏化，即，丘脑和尾状核。 这些结构的局部脑血流量（rCBBF）减少可作为这种致敏过程的标志物，并与全身性低痛阈和疼痛感知的其他改变相关，与精神病发病率或心理状态的影响无关。 该模型还假定CSF SP升高可能部分是由于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，（20）5-羟色胺代谢物5-羟基吲哚乙酸（5-HIAA）、SP、CSF白细胞数量和白细胞SP mRNA水平的CSF水平，（3）疼痛阈值和感觉辨别能力的指数以及对压痛点和控制点的痛计刺激的反应偏差，（4）心理状况和终生精神病诊断次数。 这些变量将使用（1）根据美国流变学会（ACR）标准从UAB和库珀绿色医院的流变学诊所抽取的80例FM患者进行评估（2）50名年龄、性别、教育程度和种族相当的社区居民，他们患有肌肉骨骼疼痛，符合FM的ACR标准，但在过去10年中没有因其症状寻求医疗护理的患者（“非患者”），和（3）50名具有可比人口统计学特征的社区居民，其没有肌肉骨骼疼痛，但不符合FM的ACR标准（“对照”）。 使用非患者，谁不不同于对照组的精神病发病率，将使我们能够确定是否改变水平的丘脑和尾状核的rCBF与疼痛感知和神经化学水平，无论受试者的精神病史。 本研究首次在控制心理变量的情况下，研究了rCBF与参与疼痛感知的中枢结构和神经递质以及受试者对伤害性刺激的反应之间的关系。 这项研究的结果将推进我们的知识的作用，中枢神经系统和神经内分泌和免疫异常参与改变疼痛感知FM患者和社区居民。 此外，该项目的结果可能会导致药物干预的发展，使rCBF与中枢脑结构正常化，从而减少FM患者的疼痛。

The aim of this 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 neuro- endocrine and immunologic abnormalities, characterized by decreases in cerebrospinal fluid (CSF) serotonin and increases in SCF 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 (rCBBF) 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 (1) rCBF to cortex, thalamus, and caudate nucleus, (20 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 (1) 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 cmmunity residents of comprable 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.