Abstract：
Pain is one of the most important yet poorly understood complaints in heritable connective tissue disorders (HCTDs) caused by monogenic defects in extracellular matrix molecules. This is particularly the case for the Ehlers-Danlos syndrome (EDS), paradigm collagen-related disorders. This study aimed to identify the pain signature and somatosensory characteristics in the rare classical type of EDS (cEDS) caused by defects in type V or rarely type I collagen. We used static and dynamic quantitative sensory testing and validated questionnaires in 19 individuals with cEDS and 19 matched controls. Individuals with cEDS reported clinically relevant pain/discomfort (Visual Analogue Scale ≥5/10 in 32% for average pain intensity the past month) and worse health-related quality of life. An altered somatosensory profile was found in the cEDS group with higher (P = .04) detection thresholds for vibration stimuli at the lower limb, indicating hypoesthesia, reduced thermal sensitivity with more (P < .001) paradoxical thermal sensations (PTSs), and hyperalgesia with lower pain thresholds to mechanical (P < .001) stimuli at both the upper and lower limbs and cold (P = .005) stimulation at the lower limb. Using a parallel conditioned pain modulation paradigm, the cEDS group showed significantly smaller antinociceptive responses (P-value .005-.046) suggestive of impaired endogenous pain modulation. In conclusion, individuals with cEDS report chronic pain and worse health-related quality of life and present altered somatosensory perception. This study is the first to systematically investigate pain and somatosensory characteristics in a genetically defined HCTD and provides interesting insights into the possible role of the ECM in the development and persistence of pain. PERSPECTIVE: Chronic pain compromises the quality of life in individuals with cEDS. Moreover, an altered somatosensory perception was found in the cEDS group with hypoesthesia for vibration stimuli, more PTSs, hyperalgesia for pressure stimuli, and impaired pain modulation.
摘要：
疼痛是最重要的,然而，对于由细胞外基质分子单基因缺陷引起的遗传性结缔组织疾病（HCTD）的主诉知之甚少。Ehlers-Danlos综合征（EDS）尤其如此，范例胶原蛋白相关疾病。这项研究旨在确定由V型或I型胶原蛋白缺陷引起的罕见经典型EDS（cEDS）的疼痛特征和体感特征。我们使用静态和动态定量感觉测试，并在19名cEDS个体和19名匹配对照中验证了问卷。患有cEDS的个体报告了临床相关的疼痛/不适（过去一个月平均疼痛强度为32％的VAS≥5/10）和与健康相关的生活质量较差。在cEDS组中发现了改变的体感特征，下肢振动刺激的检测阈值较高（p=0.04），表明感觉减退。热敏感性降低，具有更多(p<0.001)矛盾的热感觉，和痛觉过敏，对上肢和下肢的机械刺激（p<0.001）和对下肢的冷刺激（p=0.005）具有较低的疼痛阈值。使用并行条件性疼痛调制范例，cEDS组显示出明显较小的抗伤害感受反应(p值0.005-0.046),提示内源性疼痛调节受损.总之,患有cEDS的人报告慢性疼痛和与健康相关的生活质量较差，并表现出改变的体感知觉。这项研究是第一个系统地研究遗传定义的HCTD中的疼痛和体感特征，并为ECM在疼痛的发展和持续中的可能作用提供了有趣的见解。背景：慢性疼痛损害了Ehlers-Danlos综合征患者的生活质量，此外，在对振动刺激感觉减退的cEDS组中发现了改变的体感知觉，更矛盾的热感觉，压力刺激和疼痛调节受损的痛觉过敏。
