Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Department of Neurology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland.
Eur J Pain. 2023 Jan;27(1):72-85. doi: 10.1002/ejp.2040. Epub 2022 Oct 10.
Allodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism-based treatment strategies.
This study investigated the use of pain-autonomic readouts to objectively detect sensitization processes in CRPS.
Twenty individuals with chronic CRPS were recruited for the study alongside 16 age- and sex-matched healthy controls (HC). All individuals underwent quantitative sensory testing and neurophysiological assessments. Sympathetic skin responses (SSRs) were recorded in response to 15 pinprick and 15 noxious heat stimuli of the affected (CRPS hand/foot) and a control area (contralateral shoulder/hand).
Individuals with CRPS showed increased mechanical pain sensitivity and increased SSR amplitudes compared with HC in response to pinprick and heat stimulation of the affected (p < 0.001), but not in the control area (p > 0.05). Habituation of pinprick-induced SSRs was reduced in CRPS compared to HC in both the affected (p = 0.018) and slightly in the control area (p = 0.048). Habituation of heat-induced SSR was reduced in CRPS in the affected (p = 0.008), but not the control area (p = 0.053).
This is the first study demonstrating clinical evidence that pain-related autonomic responses may represent objective tools to quantify sensitization processes along the nociceptive neuraxis in CRPS (e.g. widespread hyperexcitability). Pain-autonomic readouts could help scrutinize mechanisms underlying the development and maintenance of chronic pain in CRPS and provide valuable metrics to detect mechanism-based treatment responses in clinical trials.
This study provides clinical evidence that autonomic measures to noxious stimuli can objectively detect sensitization processes along the nociceptive neuraxis in complex regional pain syndrome (CRPS) (e.g. widespread hyperexcitability). Pain-autonomic readouts may represent valuable tools to explore pathophysiological mechanisms in a variety of pain patients and offer novel avenues to help guide mechanism-based therapeutic strategies.
痛觉过敏和超敏反应是复杂性区域疼痛综合征（CRPS）患者的常见症状，主要归因于伤害性感受系统的敏化。目前仍缺乏用于客观评估这些超敏反应的适当诊断工具，而这些工具对于制定基于机制的治疗策略至关重要。
本研究旨在探讨使用疼痛自主反应读数来客观检测 CRPS 中的敏化过程。
本研究共招募了 20 名慢性 CRPS 患者和 16 名年龄和性别匹配的健康对照者（HC）。所有参与者均接受了定量感觉测试和神经生理评估。通过对患侧（CRPS 手/脚）和对照侧（对侧肩部/手）的 15 次刺痛和 15 次有害热刺激，记录交感皮肤反应（SSR）。
与 HC 相比，CRPS 患者在受到刺痛和热刺激时，患侧的机械痛敏和 SSR 振幅均增加（p<0.001），但在对照侧则无增加（p>0.05）。与 HC 相比，CRPS 患者在患侧的刺痛诱导 SSR 习惯化减弱（p=0.018），在对照侧略有减弱（p=0.048）。CRPS 患者在患侧的热诱导 SSR 习惯化减弱（p=0.008），但在对照侧则无减弱（p=0.053）。
这是第一项表明疼痛相关自主反应可能代表定量评估 CRPS 中伤害性感受神经元轴突上敏化过程的客观工具的临床研究（例如，广泛的过度兴奋性）。疼痛自主反应读数可以帮助深入研究 CRPS 中慢性疼痛的发展和维持的机制，并为临床试验中检测基于机制的治疗反应提供有价值的指标。
本研究提供了临床证据，表明对有害刺激的自主测量可以客观地检测 CRPS 中伤害性感受神经元轴突上的敏化过程（例如，广泛的过度兴奋性）。疼痛自主反应读数可能是探索各种疼痛患者病理生理机制的有价值工具，并为帮助指导基于机制的治疗策略提供新途径。
