Nocebo Effect on Pain-Related Autonomic Responses in a State of Experimentally-Induced Sensitization

IF 3.5 2区医学 Q1 ANESTHESIOLOGY

European Journal of Pain Pub Date : 2025-04-18 DOI:10.1002/ejp.70029

Florin Allmendinger, Jan Rosner, Thomas Egger, Paulina Simonne Scheuren, Michèle Hubli

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Abstract

Background

Enhanced pain-related autonomic responses were reported after experimentally-induced secondary mechanical hyperalgesia (SMH) in healthy individuals as well as in a variety of chronic pain cohorts. Stimulus-induced autonomic responses can also be modulated by positive and negative expectations towards the applied stimulus. This study aimed to investigate the influence of negative expectations on pain-related autonomic responses after experimentally-induced SMH.

Methods

Forty healthy participants (20 females) were recruited and assigned to a NOCEBO or a NAïVE group. Phasic skin conductance responses (SCR) and tonic background skin conductance level (SCL) were recorded in response to 10 pinprick stimuli applied to both volar forearms. On one arm, all stimuli were applied (EXP-arm) before (PRE) and after (POST) an experimental heat pain model to induce SMH. The other arm served as the control (CTRL-arm). The NOCEBO group was instructed that the stimuli will be ‘more intense and painful’ in the POST-assessment. The NAïVE group did not receive any instructions. Pain ratings were matched to a numeric rating scale 4 across all assessments to control for subjective pain perception.

Results

Only the combination of induced SMH and negative expectation (i.e., EXP-arm in the NOCEBO group) increased the pinprick-evoked phasic SCRs (p < 0.001) from PRE to POST. Tonic background SCL increased from PRE to POST (p < 0.01) independent of stimulation area (i.e., EXP-arm or CTRL-arm) or group (i.e., NOCEBO or NAïVE).

Conclusions

These results demonstrate facilitatory effects of top-down modulatory processes (i.e., negative expectations) on pain-related autonomic responses after experimentally-induced SMH.

Significance

This study showed a facilitatory effect of negative expectation on enhanced pain-related autonomic responses in a state of experimentally-induced sensitisation in healthy participants. Hence, pain-related autonomic responses are shaped by both bottom-up (nociceptive input) and top-down (expectation) modulatory processes. This leads to the clinical implication that increased pain-related autonomic responses reported in individuals with chronic pain might not solely reflect pain hypersensitivities through nociceptive sensitisation, but also exaggerated negative expectation.

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实验诱导致敏状态下反安慰剂对疼痛相关自主神经反应的影响

在健康个体和各种慢性疼痛人群中，实验诱导的继发性机械性痛觉过敏（SMH）后，疼痛相关自主神经反应增强。刺激诱导的自主神经反应也可以通过对施加刺激的积极和消极期望来调节。本研究旨在探讨消极预期对实验性SMH后疼痛相关自主神经反应的影响。方法招募40名健康受试者（20名女性），分为NOCEBO组和NAïVE组。记录两前臂掌侧10次针刺刺激下的皮肤电相反应（SCR）和皮肤电背景强直水平（SCL）。在一只手臂上，在实验热痛模型之前（PRE）和之后（POST）施加所有刺激（exp -臂）以诱导SMH。另一只手臂作为对照组（CTRL-arm）。NOCEBO组被告知，在后评估中，刺激会“更强烈、更痛苦”。NAïVE组没有收到任何指示。在所有评估中，疼痛评分与数字评分量表相匹配，以控制主观疼痛感知。结果只有诱导的SMH和负期望（即NOCEBO组的exp臂）联合使用才能使针刺诱发的相性SCRs从PRE到POST增加（p < 0.001）。强直性背景SCL在刺激前至刺激后升高（p < 0.01），与刺激区域（即EXP-arm或CTRL-arm）或组（即NOCEBO或NAïVE）无关。结论实验结果表明，自上而下的调节过程（即负面预期）对实验性SMH后疼痛相关的自主神经反应具有促进作用。本研究表明，在实验诱导致敏状态下，负面期望对健康受试者疼痛相关自主神经反应的增强具有促进作用。因此，与疼痛相关的自主神经反应是由自下而上（伤害性输入）和自上而下（期望）调节过程共同形成的。这导致临床意义，在慢性疼痛患者中报告的疼痛相关自主神经反应的增加可能不仅仅反映了通过伤害性敏化产生的疼痛超敏反应，还反映了夸大的负面预期。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Pain 医学-临床神经学

CiteScore

7.50

自引率

5.60%

发文量

163

审稿时长

4-8 weeks

期刊介绍： European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.