Pathophysiology of Small-Fiber Sensory System in Parkinson's Disease: Skin Innervation and Contact Heat Evoked Potential.
Pathophysiology of Small-Fiber Sensory System in Parkinson's Disease: Skin Innervation and Contact Heat Evoked Potential.
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DOI：
10.1097/md.0000000000003058
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发表时间：
2016-03
期刊：
影响因子：
1.6
通讯作者：
Hsieh ST
中科院分区：
文献类型：
--
作者：
Lin CH;Chao CC;Wu SW;Hsieh PC;Feng FP;Lin YH;Chen YM;Wu RM;Hsieh ST
感觉症状是帕金森病 (PD) 患者常见的非运动症状。然而，很少有研究全面探讨帕金森病中热痛感受通路的生理学和病理学。我们的目的是研究热痛感受通路在帕金森病中的参与情况。研究招募了 28 名没有神经病症状和全身性疾病的 PD 患者（16 名男性，平均年龄和标准差为 65.6±10.7 岁），并与 23 名年龄和性别匹配的对照受试者（12 名男性，平均年龄和标准差为 65.1±9.9 岁）进行比较。我们进行了皮肤活检、接触热诱发电位 (CHEP) 和定量感觉测试 (QST)，以研究热伤害感受通路在帕金森病中的参与情况。 PD持续时间为7.1±3.2年（范围2-17年），停药期UPDRS第III部分评分为25.6±9.7（范围10-48）。与对照组相比，PD患者的表皮内神经纤维（IENF）密度（2.48 ± 1.65 vs 6.36 ± 3.19 纤维/mm，P < 0.001）和CHEP波幅（18.02 ± 10.23 vs）降低33.28 ±10.48 μV，P < 0.001）。 23 名患者 (82.1%) 的 IENF 密度异常，18 名患者 (64.3%) 的 CHEP 异常。 9 名患者（32.1%）的足部热阈值异常。总共 27 名患者 (96.4%) 的 IENF、CHEP 或足部热阈值至少有 1 处异常，表明小纤维神经系统存在功能障碍。在对照受试者中，CHEP 幅度与 IENF 密度线性相关 (P < 0.001)。相反，这种关系在PD中消失（P = 0.312），并且CHEP波幅与PD的运动严重程度呈负相关，与年龄、性别和抗PD药物剂量无关（P = 0.036），这表明除了外周小纤维神经外，中枢成分对PD中的热伤害感受系统也有影响。本研究表明，外周和中枢水平的小纤维感觉系统受损是 PD 的一个内在特征，皮肤活检、CHEP 和 QST 为评估此类功能障碍提供了一种完整的方法。
Sensory symptoms are frequent nonmotor complaints in patients with Parkinson's disease (PD). However, few investigations integrally explored the physiology and pathology of the thermonociceptive pathway in PD. We aim to investigate the involvement of the thermonociceptive pathway in PD. Twenty-eight PD patients (16 men, with a mean age and standard deviation of 65.6 ± 10.7 years) free of neuropathic symptoms and systemic disorders were recruited for the study and compared to 23 age- and gender-matched control subjects (12 men, with a mean age and standard deviation of 65.1 ± 9.9 years). We performed skin biopsy, contact heat-evoked potential (CHEP), and quantitative sensory tests (QST) to study the involvement of the thermonociceptive pathway in PD. The duration of PD was 7.1 ± 3.2 (range 2–17 years) years and the UPDRS part III score was 25.6 ± 9.7 (range 10–48) during the off period. Compared to control subjects, PD patients had reduced intra-epidermal nerve fiber (IENF) density (2.48 ± 1.65 vs 6.36 ± 3.19 fibers/mm, P < 0.001) and CHEP amplitude (18.02 ± 10.23 vs 33.28 ± 10.48 μV, P < 0.001). Twenty-three patients (82.1%) had abnormal IENF densities and 18 (64.3%) had abnormal CHEP. Nine patients (32.1%) had abnormal thermal thresholds in the feet. In total 27 patients (96.4%) had at least 1 abnormality in IENF, CHEP, or thermal thresholds of the foot, indicating dysfunctions in the small-fiber nerve system. In control subjects, CHEP amplitude linearly correlated with IENF density (P < 0.001). In contrast, this relationship disappeared in PD (P = 0.312) and CHEP amplitude was negatively correlated with motor severity of PD independent of age, gender, and anti-PD medication dose (P = 0.036), suggesting the influences of central components on thermonociceptive systems in addition to peripheral small-fiber nerves in PD. The present study suggested impairment of small-fiber sensory system at both peripheral and central levels is an intrinsic feature of PD, and skin biopsy, CHEP, and QST provided an integral approach for assessing such dysfunctions.