FIBROMYALGIA: CENTRAL FACTORS IN ITS ETIOPATHOGENESIS

有大量证据表明，纤维肌痛（FM）患者存在异常的疼痛敏感性和功能性脑活动。鉴于神经内分泌轴功能异常和压力加剧FM症状的倾向，有证据表明FM可能是一种与压力相关的疾病。然而，到目前为止，还没有研究者研究过压力对FM患者和对照组疼痛敏感性或功能性脑活动的影响。我们提出了一项研究，以测试从FM异常疼痛感知模型中得出的10个假设，这些假设涉及应激对疼痛敏感性和处理疼痛的大脑结构功能活动的影响。我们将评估有害热刺激和个人相关的压力图像对疼痛阈值和耐受性的影响，感觉强度和不愉快的幅度估计，以及处理疼痛的感觉和情感维度的大脑结构的功能活动。我们将对120名非抑郁的右撇子女性和60名非抑郁的健康对照女性进行这些评估程序。患者将根据症状发作（创伤性与隐匿性）分为两组。我们假设，与对照组相比，在有害热刺激期间，患者将(a)产生更高的疼痛强度和不愉快程度；(b)显示了一种异常的大脑激活模式，其特征是双侧体感觉皮层区域脑血流量（rCBF）增加，同侧前扣带皮层（AC）增加。我们还假设，在暴露于与个人相关的、有压力的图像时，与对照组相比，患者将显示：(a)唾液皮质醇的增加较小；(b)血压、脉搏率、热痛强度和不愉快程度的更大增加，以及热痛引起的对侧和同侧体感觉皮层以及同侧交流皮层的变化。这项研究将使我们能够评估应激对FM患者疼痛感知和功能性脑活动的影响，而不受情感障碍的影响。结果将推进我们对压力对异常疼痛敏感性的影响的认识，以及在FM患者中这种敏感性的生物学过程。因此，这项研究的结果可能最终导致改进的药物干预，可能使FM中产生疼痛症状的中枢生物学异常正常化。

There is substantial evidence of abnormal pain sensitivity and functional brain activity in patients with fibromyalgia (FM). It has been suggested that FM may be a stress-related disorder, given the evidence of abnormal function of the neuroendocrine axes and the tendency of stress to exacerbate FM symptoms. However, no investigator to date has examined the effects of stress on pain sensitivity or functional brain activity in FM patients and controls. We propose study to test 10 hypotheses derived from our model of abnormal pain perception in FM regarding the effects of stress on pain sensitivity and functional activity in brain structures that process pain. We will assess the effects of noxious thermal stimulation and personally relevant, stressful imagery on pain thresholds and tolerance, magnitude estimates of sensory intensity and unpleasantness, and functional activity of brain structures that process the sensory and affective dimensions of pain. We will perform these evaluation procedures with 120, non- depressed, right-handed women with FM and 60, non-depressed, healthy control women. The patients will be classified in one of two groups according to symptom onset (traumatic vs. insidious). We hypothesize that during noxious thermal stimulation, patients, compared to controls, will (a) produce higher ratings of pain intensity and unpleasantness; and (b) show an abnormal pattern of brain activation characterized by bilateral increases in regional cerebral blood flow (rCBF) in the somatosensory cortices and increases in the ipsilateral anterior cingulate (AC) cortex. We also hypothesize that during exposure to personally relevant, stressful imagery, patients, compared to controls will show (a) smaller increases in salivary cortisol; and (b) greater increases in blood pressure, pulse rate, thermal pain intensity and unpleasantness ratings, and thermal pain-induced change in the contralateral and ipsilateral somatosensory cortices as well as in the ipsilateral AC cortex. This study will allow us to assess the effects of stress on pain perception and functional brain activity in patients with FM independently of the influence of affective disorders. The results will advance our knowledge regarding the effects of stress on abnormal pain sensitivity and the biologic processes that underlie this sensitivity in persons with FM. Thus, the results of the study may eventually lead to improved pharmacologic inteventions that may normalize the central biologic abnormalities that produce painful symptoms in FM.