title: Psychophysiological responses to pain identify reproducible human clusters.
abstract: 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.
authors.affiliation: 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.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Farmer
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Coen
authors.forename: Michiko
authors.initials: M
authors.lastname: Kano
authors.forename: Peter A
authors.initials: PA
authors.lastname: Paine
authors.forename: Mustafa
authors.initials: M
authors.lastname: Shwahdi
authors.forename: Jafar
authors.initials: J
authors.lastname: Jafari
authors.forename: Jessin
authors.initials: J
authors.lastname: Kishor
authors.forename: Sian F
authors.initials: SF
authors.lastname: Worthen
authors.forename: Holly E
authors.initials: HE
authors.lastname: Rossiter
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
authors.forename: Steven C R
authors.initials: SCR
authors.lastname: Williams
authors.forename: Michael
authors.initials: M
authors.lastname: Brammer
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Giampietro
authors.forename: Joanne
authors.initials: J
authors.lastname: Droney
authors.forename: Julia
authors.initials: J
authors.lastname: Riley
authors.forename: Paul L
authors.initials: PL
authors.lastname: Furlong
authors.forename: Charles H
authors.initials: CH
authors.lastname: Knowles
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
authors.forename: Qasim
authors.initials: Q
authors.lastname: Aziz
mesh_terms: D000328:Adult; D001007:Anxiety / Q000523:psychology; D001341:Autonomic Nervous System / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology; D004247:DNA / Q000235:genetics; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D058748:Pain Perception / Q000502:physiology; D010551:Personality; D010556:Personality Tests; D011603:Psychophysiology; D015203:Reproducibility of Results; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D059265:Visceral Pain / Q000503:physiopathology / Q000523:psychology; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA; D006854:Hydrocortisone
keywords: Autonomic nervous system; Hypothalamic-pituitary-adrenal axis; Personality traits; Serotonin transporter genotype; Somatic pain; Visceral pain