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在实验性诱导敏化状态下,安慰剂对疼痛相关自主反应的影响。

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

作者信息

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

机构信息

Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.

Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

出版信息

Eur J Pain. 2025 May;29(5):e70029. doi: 10.1002/ejp.70029.

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.

摘要

背景

在健康个体以及各种慢性疼痛患者群体中,实验性诱导的继发性机械性痛觉过敏(SMH)后,与疼痛相关的自主反应增强。刺激诱导的自主反应也可受到对所施加刺激的积极和消极预期的调节。本研究旨在调查消极预期对实验性诱导SMH后与疼痛相关的自主反应的影响。

方法

招募40名健康参与者(20名女性),并将其分为安慰剂组或单纯组。记录对双侧前臂掌侧施加的10次针刺刺激所产生的阶段性皮肤电导反应(SCR)和持续性背景皮肤电导水平(SCL)。在一只手臂上,在实验性热痛模型诱导SMH之前(PRE)和之后(POST)施加所有刺激(实验臂)。另一只手臂作为对照(对照臂)。安慰剂组被告知在POST评估中刺激会“更强烈且更疼痛”。单纯组未接受任何指示。在所有评估中,疼痛评分与数字评分量表4相匹配,以控制主观疼痛感知。

结果

只有诱导的SMH和消极预期的组合(即安慰剂组的实验臂)使针刺诱发的阶段性SCR从PRE到POST增加(p < 0.001)。持续性背景SCL从PRE到POST增加(p < 0.01),与刺激区域(即实验臂或对照臂)或组(即安慰剂组或单纯组)无关。

结论

这些结果表明自上而下的调节过程(即消极预期)对实验性诱导SMH后与疼痛相关的自主反应具有促进作用。

意义

本研究表明,在健康参与者实验性诱导的致敏状态下,消极预期对增强的与疼痛相关的自主反应具有促进作用。因此,与疼痛相关的自主反应受到自下而上(伤害性输入)和自上而下(预期)调节过程的影响。这导致了一个临床意义,即慢性疼痛个体中报告的与疼痛相关的自主反应增加可能不仅反映了通过伤害性致敏引起的疼痛超敏反应,还反映了夸大的消极预期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0633/12008480/6639b03ea78b/EJP-29-0-g004.jpg

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本文引用的文献

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