Pain processing and pain perception in the human brain: a neural signals approach

人脑的疼痛处理和疼痛感知：神经信号方法

• 批准号: MR/M013901/1
• 负责人: Patrick Haggard
• 金额: $ 66.74万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM013901%2F1
• 关键词: Pain; processing; pain; perception; human

Pain is an almost universal experience. Its importance for health, well-being and disease processes is undeniable. One can experience more or less pain, and measuring pain intensity is important in diagnosis, assessment and therapy. However, this measurement is surprisingly difficult, because pain levels depend on complex factors such as expectation, attention, and even personality. Moreover, robust, valid measures of pain intensity are elusive. Current methods, such as numerical pain rating scales, rely strongly on patients' verbal understanding - e.g., the phrase "worst pain imaginable" is generally used to define the top of the scale. Perhaps for these reasons, ratings show notoriously poor correlation with the energy of a noxious stimulus, and also with activation of putative 'pain centres' or 'pain networks' in the brain.This project develops a novel approach to understanding pain perception. Using a state-of-the-art feedback-controlled laser stimulator, we expose the skin on the back of the hand of healthy volunteers to brief, quantified pulses of radiant heat, causing a sharp 'pinprick' pain. This reflects signals in a specific neurophysiological pain pathway ("A-delta pathway"). Participants are stimulated randomly with either of two energies, both above the individual's threshold to activate the A-delta pathway. They judge whether they experienced 'higher' or 'lower' intensity. We use standard methods to calculate two distinct aspects of pain perception: the SENSITIVITY with which a person's judgements track the actual stimulation energy, and their BIAS in preferring to respond 'higher', or 'lower', irrespective of actual stimulation energy. For example, someone who simply fears strong pain might judge ALL pain stimuli as 'higher' intensity: they would then show strong bias and low sensitivity.We also record the brain activity evoked by laser stimulation, using EEG electrodes non-invasively placed on the scalp. By dividing the distribution of EEG amplitudes in two at different cutoff points, we can simulate how effective the EEG signal at that particular moment would be in classifying the higher and lower intensity stimuli. We will thus identify the components of the brain's response to noxious stimulation that best approximate the sensitivity and bias components of pain perception. This provides a novel, well-controlled, physiologically-specific, and fully objective method to search for the neural basis of pain perception. It does not require any subjective definition or instruction regarding what counts as 'pain', and merely requires participants to judge whether a stimulus is more or less intense. By testing a large sample of participants, we address individual differences between people in pain perception. We may identify psychological profiles associated with high and low pain bias, and with high and low pain sensitivity.Two further large experiments leverage these important methodological developments. Experiment 2 aims to show how our method can be used to quantify and understand the potency of a popular analgesic drug (remifentanil). Double-blind infusions of drug or placebo are compared to address whether the drug influences bias or sensitivity, and which EEG components underlie this change.Experiment 3 uses these new measurement approaches to investigate the basis of the well-known placebo effect - perhaps the most striking finding in pain research. Participants learn that a specific visual stimulus, presented before laser stimulation, predicts whether the next stimulus will be more or less intense. Again, we assess whether this predictive cue changes sensitivity or bias. We will identify the EEG components that are responsible for how the cue influences these two aspects of pain perception.Overall, the results provide a novel and objective approach to pain perception, useful for future clinical studies of pain and analgesia.

疼痛几乎是一种普遍的体验。它对健康、福祉和疾病进程的重要性是不可否认的。一个人可以经历或多或少的疼痛，测量疼痛强度在诊断，评估和治疗中很重要。然而，这种测量是令人惊讶的困难，因为疼痛程度取决于复杂的因素，如期望，注意力，甚至个性。此外，对疼痛强度的可靠、有效的测量是难以捉摸的。目前的方法，如数字疼痛评级量表，强烈依赖于患者的口头理解-例如，短语“可以想象的最严重的疼痛”通常用于定义等级的顶部。也许正是由于这些原因，评级与有害刺激的能量以及大脑中假定的“疼痛中心”或“疼痛网络”的激活之间的相关性非常差。该项目开发了一种理解疼痛感知的新方法。使用最先进的反馈控制激光刺激器，我们将健康志愿者手背上的皮肤暴露在短暂的、量化的辐射热脉冲下，引起尖锐的“针刺”疼痛。这反映了特定神经生理疼痛通路（“A-δ通路”）中的信号。参与者被随机刺激两种能量中的任何一种，这两种能量都高于个人激活A-δ通路的阈值。他们判断他们是否经历了“更高”或“更低”的强度。我们使用标准方法来计算疼痛感知的两个不同方面：一个人的判断跟踪实际刺激能量的灵敏度，以及他们的偏见，无论实际刺激能量如何，他们都倾向于响应“更高”或“更低”。例如，一个仅仅害怕强烈疼痛的人可能会把所有的疼痛刺激都判断为“更高”的强度：他们会表现出强烈的偏见和低敏感性。我们还记录了激光刺激引起的大脑活动，使用非侵入性放置在头皮上的EEG电极。通过在不同的截止点处将EEG幅度的分布分为两部分，我们可以模拟在该特定时刻的EEG信号在分类较高和较低强度刺激时的有效性。因此，我们将确定大脑对伤害性刺激的反应的组成部分，这些组成部分最接近疼痛感知的敏感性和偏差。这提供了一种新颖、受控、生理特定且完全客观的方法来寻找疼痛感知的神经基础。它不需要任何关于什么是“疼痛”的主观定义或指导，只需要参与者判断刺激是否更强烈或更弱。通过测试大样本的参与者，我们解决了人与人之间在疼痛感知方面的个体差异。我们可以识别出与高和低疼痛偏差以及高和低疼痛敏感性相关的心理特征，进一步的两个大型实验利用了这些重要的方法学发展。实验2旨在展示我们的方法如何用于量化和了解一种流行的镇痛药物（瑞芬太尼）的效力。双盲输注药物或安慰剂进行比较，以解决药物是否影响偏倚或敏感性，以及EEG成分的基础上，这种变化。实验3使用这些新的测量方法来调查众所周知的安慰剂效应的基础-也许是最引人注目的发现在疼痛研究。参与者了解到，在激光刺激之前呈现的特定视觉刺激可以预测下一个刺激是否会更强烈或更弱。同样，我们评估这种预测线索是否会改变敏感性或偏差。我们将确定脑电成分，负责如何线索影响这两个方面的疼痛perception.Overall，结果提供了一种新的和客观的方法来疼痛知觉，有助于未来的疼痛和镇痛的临床研究。

项目成果

Thermonociceptive interaction: interchannel pain modulation occurs before intrachannel convergence of warmth.

热痛感受相互作用：通道间疼痛调节发生在通道内温暖收敛之前。

• DOI: 10.1152/jn.00341.2018
• 发表时间: 2019
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Cataldo A

"Lacking warmth": Alexithymia trait is related to warm-specific thermal somatosensory processing.

• DOI: 10.1016/j.biopsycho.2017.07.012
• 发表时间: 2017-09
• 期刊: Biological psychology
• 影响因子: 2.6
• 作者: Borhani K;Làdavas E;Fotopoulou A;Haggard P
• 通讯作者: Haggard P

Which way is down? Visual and tactile verticality perception in expert dancers and non-experts.

• DOI: 10.1016/j.neuropsychologia.2020.107546
• 发表时间: 2020-09
• 期刊: Neuropsychologia
• 影响因子: 2.6
• 作者: Beck B;Saramandi A;Ferrè ER;Haggard P
• 通讯作者: Haggard P

Touch inhibits touch: sanshool-induced paradoxical tingling reveals perceptual interaction between somatosensory submodalities.

• DOI: 10.1098/rspb.2020.2914
• 发表时间: 2021-01-27
• 期刊: Proceedings. Biological sciences
• 作者: Cataldo A;Hagura N;Hyder Y;Haggard P
• 通讯作者: Haggard P