Psychophysiological responses to pain identify reproducible human clusters

TY - JOUR

T1 - Psychophysiological responses to pain identify reproducible human clusters

AU - Farmer, Adam D.

AU - Coen, Steven J.

AU - Kano, Michiko

AU - Paine, Peter A.

AU - Shwahdi, Mustafa

AU - Jafari, Jafar

AU - Kishor, Jessin

AU - Worthen, Sian F.

AU - Rossiter, Holly E.

AU - Kumari, Veena

AU - Williams, Steven C. R.

AU - Brammer, Michael

AU - Giampietro, Vincent P.

AU - Droney, Joanne

AU - Riley, Julia

AU - Furlong, Paul L.

AU - Knowles, Charles H.

AU - Lightman, Stafford L.

AU - Aziz, Qasim

PY - 2013/11

Y1 - 2013/11

N2 - 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 1 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.

AB - 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 1 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.

KW - Visceral pain

KW - Somatic pain

KW - Autonomic nervous system

KW - Hypothalamic-pituitary-adrenal axis

KW - Personality traits

KW - Serotonin transporter genotype

KW - IRRITABLE-BOWEL-SYNDROME

KW - HEART-RATE-VARIABILITY

KW - TRANSPORTER GENE POLYMORPHISM

KW - CARDIAC VAGAL TONE

KW - SEROTONIN-TRANSPORTER

KW - INDIVIDUAL-DIFFERENCES

KW - VISCERAL SENSATION

KW - RECTAL DISTENSION

KW - ENDOGENOUS PAIN

KW - NERVOUS-SYSTEM

U2 - 10.1016/j.pain.2013.05.016

DO - 10.1016/j.pain.2013.05.016

M3 - Article

C2 - 23714265

VL - 154

SP - 2266

EP - 2276

JO - Pain

JF - Pain

IS - 11

M1 - N/A

ER -