Centre for Digestive Diseases, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK Behavioural Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Gastrointestinal Sciences, University of Manchester, Manchester, UK Aston Brain Centre, School of Life and Health Sciences, Aston University, Birmingham, UK Department of Psychology, Institute of Psychiatry, King's College London, London, UK Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK National Heart and Lung Institute, Imperial College London, London, UK Henry Wellcome Laboratories for Integrative Neuroscience & Endocrinology, University of Bristol, Bristol, UK.
Pain. 2013 Nov;154(11):2266-2276. doi: 10.1016/j.pain.2013.05.016. Epub 2013 May 25.
Pain is a ubiquitous yet highly variable experience. The psychophysiological and genetic factors responsible for this variability remain unresolved. We hypothesised the existence of distinct human pain clusters (PCs) composed of distinct psychophysiological and genetic profiles coupled with differences in the perception and the brain processing of pain. We studied 120 healthy subjects in whom the baseline personality and anxiety traits and the serotonin transporter-linked polymorphic region (5-HTTLPR) genotype were measured. Real-time autonomic nervous system parameters and serum cortisol were measured at baseline and after standardised visceral and somatic pain stimuli. Brain processing reactions to visceral pain were studied in 29 subjects using functional magnetic resonance imaging (fMRI). The reproducibility of the psychophysiological responses to pain was assessed at year. In group analysis, visceral and somatic pain caused an expected increase in sympathetic and cortisol responses and activated the pain matrix according to fMRI studies. However, using cluster analysis, we found 2 reproducible PCs: at baseline, PC1 had higher neuroticism/anxiety scores (P ≤ 0.01); greater sympathetic tone (P<0.05); and higher cortisol levels (P ≤ 0.001). During pain, less stimulus was tolerated (P ≤ 0.01), and there was an increase in parasympathetic tone (P ≤ 0.05). The 5-HTTLPR short allele was over-represented (P ≤ 0.005). PC2 had the converse profile at baseline and during pain. Brain activity differed (P ≤ 0.001); greater activity occurred in the left frontal cortex in PC1, whereas PC2 showed greater activity in the right medial/frontal cortex and right anterior insula. In health, 2 distinct reproducible PCs exist in humans. In the future, PC characterization may help to identify subjects at risk for developing chronic pain and may reduce variability in brain imaging studies.
疼痛是一种普遍存在但高度可变的体验。导致这种可变性的心理生理和遗传因素仍未解决。我们假设存在不同的人类疼痛簇（PC），它们由不同的心理生理和遗传特征组成，同时伴有疼痛感知和大脑处理方面的差异。我们研究了 120 名健康受试者，测量了他们的基线人格特质和焦虑特质以及血清素转运体连接多态性区域（5-HTTLPR）基因型。在基线和标准内脏和躯体疼痛刺激后测量实时自主神经系统参数和血清皮质醇。在 29 名受试者中使用功能磁共振成像（fMRI）研究内脏疼痛的大脑处理反应。在一年内评估对疼痛的心理生理反应的可重复性。在组分析中，内脏和躯体疼痛引起交感神经和皮质醇反应的预期增加，并根据 fMRI 研究激活疼痛矩阵。然而，使用聚类分析，我们发现了 2 个可重复的 PC：在基线时，PC1 具有更高的神经质/焦虑评分（P ≤ 0.01）；更高的交感神经张力（P <0.05）；和更高的皮质醇水平（P ≤ 0.001）。在疼痛期间，可耐受的刺激减少（P ≤ 0.01），并且副交感神经张力增加（P ≤ 0.05）。5-HTTLPR 短等位基因过度表达（P ≤ 0.005）。PC2 在基线和疼痛期间具有相反的特征。大脑活动不同（P ≤ 0.001）；在 PC1 中，左额叶皮质活动增加，而在 PC2 中，右内侧/额叶皮质和右前岛叶活动增加。在健康状态下，人类存在 2 个不同的可重复 PC。将来，PC 特征描述可能有助于识别易患慢性疼痛的受试者，并减少大脑成像研究的变异性。
