FIBROMYALGIA--CENTRAL FACTORS IN ITS ETIOPATHOGENESIS

这项研究的目的是为了更好地了解纤维肌痛(FM)痛觉改变的发病机制中涉及的中心因素。我们将检验来自一个模型的六个假说，该模型假设神经内分泌和免疫异常，以脑脊液(CSF)5-羟色胺减少和SCF P物质(SP)增加为特征，导致参与痛觉的中枢神经系统结构(即丘脑和尾状核)敏化。流向这些结构的局部脑血流量(RCBBF)的减少是这种敏化过程的标志，并与普遍的低痛阈值和其他痛觉变化有关，与精神疾病或心理状态的影响无关。该模型还假设，脑脊液SP升高的部分原因可能是脑脊液白细胞产生SP信使(M)RNA。我们建议测量(1)皮质、丘脑和尾状核的rCBF，(20)脑脊液中5-羟色胺代谢产物5-羟吲哚乙酸(5-HIAA)的水平，P物质(SP)，脑脊液白细胞数和白细胞P物质(SP)m RNA水平，(3)痛阈值和感觉辨别能力指数以及对压痛点和控制点的反应偏差，(4)心理状态和终生精神疾病诊断次数。这些变量将使用(1)80名来自UAB和库珀格林医院风湿病诊所的美国风湿病学会(ACR)标准的FM患者(“患者”)，(2)50名年龄、性别、教育程度和种族相似的具有肌肉骨骼疼痛的社区居民，他们符合FM的ACR标准，但在过去10年中没有因其症状寻求医疗护理(“非患者”)，以及(3)50名具有类似人口统计学特征但没有肌肉骨骼疼痛的社区居民(“对照”)。使用非患者，他们在精神发病率方面与对照组没有区别，将使我们能够确定丘脑和尾状核rCBF水平的变化是否与疼痛感觉和神经化学水平有关，而不考虑受试者的精神病史。这项研究首次研究了rCBF与中枢结构和涉及疼痛感知的神经递质之间的关系，以及受试者在控制心理变量的同时对有害刺激的反应。这项研究的结果将促进我们对中枢神经系统、神经内分泌和免疫异常在FM患者和社区居民痛觉改变中的作用的了解。此外，该项目的结果可能导致开发药物干预措施，使中央大脑结构的rCBF正常化，从而减轻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.