Pain-related Fear as a Facilitator of Nocebo Hyperalgesia: An Experimental Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 2
- 主要终点
- Magnitude of nocebo hyperalgesia
研究概览
简要总结
Nocebo hyperalgesia is characterized by adverse pain outcomes, induced by patients' expectations. In the lab, nocebo effects are commonly studied via classical conditioning, a method that employs pairings of neutral cues/treatments with different pain intensities to install differential pain-related expectations. In such conditioning experiments, participants are typically taught that a (sham) treatment exaggerates their pain, by surreptitiously administering high intensity (e.g. pain) stimuli in combination with this treatment. Verbal suggestions are also often used to inform participants of the supposed adverse effects of such treatments. In nocebo studies, higher pain levels and suggestions that are of more threatening nature may induce fear, thereby adding a crucial element to the experimental manipulation. Since nocebo effects are hypothesized to arise in clinical settings due to a combination of several psychological and cognitive mechanisms, it is important to study the role that factors such as higher pain levels, conditioned pain-related fear, or more threatening verbal suggestions may play in the formation of nocebo hyperalgesia. To date, no studies have focused on the fear-inducing effect that different pain intensities or verbal threat suggestions may have and how this fear, in turn, may strengthen the acquisition of nocebo effects. This study aims to investigate whether higher pain intensity or higher pain-related fear induced via threatening suggestions facilitate the acquisition and hinder subsequent extinction of nocebo hyperalgesia. This study will be conducted at Leiden University.
详细描述
The investigators expect that higher pain intensity and/or higher pain-related fear induced via threatening suggestions will lead to stronger acquisition of nocebo hyperalgesia and/or more durable nocebo hyperalgesia after extinction.
Main outcome variables:
- The magnitude of induced nocebo hyperalgesia is defined as the difference in pain ratings for the first nocebo trial compared to the first control trial of the extinction phase.
- The reduction of nocebo hyperalgesia is defined as the change in reported pain between the first and last nocebo trial of the extinction phase.
- Fear levels (for mediation analyses) are measured via eye-blink startle modulation and self-reported fear during nocebo trials (relative to control trials).
For EMG analyses this study follows typical pre-processing of EMG recordings, similar to previous studies. The EMG signal will be digitized at 1,000 Hz from 200 ms before the startle probe until 1,500 ms after probe onset. The startle probe is a 100 dBA burst of white noise with instantaneous rise time presented binaurally for 100 ms through earphones. Each 2-4 consecutive startle probe responses of the same cue (nocebo vs control) will be averaged for further analyses. Participants who exhibited a startle response in less than 20% of trials in the first half of induction will be labeled as non-responders. Trials during which, for example, baseline is higher than startle response peak due to an occasional blink before the probe presentation, will be labelled as non-response or reject trials.
- Main planned analyses:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
A double-blind randomization list (stratified for gender) was created by an independent researcher. Complete blinding of the researchers during the experiment is not possible due to the nature of the conditioning paradigms. However, in this study blinding is optimized: the researchers are informed of the (conditioning) group to which participants are allocated after their final inclusion to the study and after the start of the experiment.
入排标准
- 年龄范围
- 17 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 17 - 35 years
- •Good understanding of the English language
- •Normal or corrected to normal vision
排除标准
- •Ever having experienced serious medical or psychiatric conditions (e.g., heart or lung disease, panic attacks, drug addiction, clinical depression),
- •Ever having experienced chronic pain complaints (pain for more than 6 months),
- •Experiencing acute physical pain (e.g., headache; above 3 on a 10-point NRS scale), or having used pain medication on the day of testing,
- •Pregnancy or breastfeeding,
- •Having recent injuries to the wrists or arms on the day of testing,
- •Previous participation in this or similar studies (e.g., using conditioning or thermal pain).
- •Having consumed psychotropic medication, recreational drugs, analgesic medication, or more than 3 units of alcohol, in the 24 hours prior to the study appointment.
- •After inclusion, participants who do not reach a sensation of high pain (at least 6 on the NRS) with the highest administered temperature or participants who appear unable to distinguish between moderate and high pain stimuli (reporting at least a mean difference of 1.5 NRS points between nocebo and control trials during induction) will also be excluded.
结局指标
主要结局
Magnitude of nocebo hyperalgesia
时间窗: On the testing day, in the first trials of the extinction phase
The magnitude of induced nocebo hyperalgesia is defined as the difference in pain ratings for the first nocebo trial compared to the first control trial of the extinction phase.
次要结局
- Reduction of nocebo hyperalgesia(On the testing day, in the extinction phase)
研究者
AWMEvers
Principal Investigator
Leiden University Medical Center