Small fibre pathology in patients with fibromyalgia syndrome
Small fibre pathology in patients with fibromyalgia syndrome
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DOI：
10.1093/brain/awt053
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发表时间：
2013-06-01
期刊：
影响因子：
14.5
通讯作者：
Sommer, Claudia
中科院分区：
文献类型：
--
作者：
Uceyler, Nurcan;Zeller, Daniel;Sommer, Claudia
纤维肌痛综合征是一种临床特征良好的慢性疼痛状况，具有很高的社会经济影响。虽然病理生理学尚不清楚，但越来越多的证据表明纤维肌痛综合征患者存在神经系统功能障碍。在这项病例对照研究中，我们调查了25例纤维肌痛综合征患者的小神经纤维的功能和形态。患者接受了全面的神经和神经生理学评估。我们通过定量感觉测试和疼痛相关诱发电位检查小纤维功能，并在小腿和大腿上部的皮肤穿刺活检中定量表皮内神经纤维密度和再生表皮内神经纤维。研究结果与10名无疼痛的单极抑郁症患者的数据进行了比较，并与年龄和性别相匹配的健康对照组进行了比较。所有患者的神经学和标准神经生理学检查均正常，不包括大纤维多发性神经病。纤维肌痛综合征患者在神经病理性疼痛问卷中的得分高于抑郁症患者和对照组（均P < 0.001）。与对照组相比，纤维肌痛综合征患者的小纤维功能受损，定量感觉测试中的冷、热检测阈值升高（P < 0.001），而抑郁症患者无此现象。对疼痛相关诱发电位的研究显示，与抑郁症患者和对照组相比，纤维肌痛综合征患者在足部刺激时N1潜伏期增加（P <0.001），在面部、手部和足部刺激时疼痛相关诱发电位振幅降低（P < 0.001），表明小纤维或其中枢传入异常。在皮肤活检中，与对照组相比，纤维肌痛综合征患者小腿和大腿上部的总（P < 0.001）和再生表皮内神经纤维（P < 0.01）减少。因此，与抑郁症患者和健康对照受试者相比，纤维肌痛综合征患者的皮肤样本中真皮无髓神经纤维束减少，而有髓神经纤维则幸免。使用的所有三种方法都支持纤维肌痛综合征患者小纤维功能受损的概念，指出纤维肌痛综合征疼痛的神经病理性质。
Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.