Psychophysiological responses to pain identify reproducible human clusters

Adam D. Farmer, Steven J. Coen, Michiko Kano, Peter A. Paine, Mustafa Shwahdi, Jafar Jafari, Jessin Kishor, Sian F. Worthen, Holly E. Rossiter, Veena Kumari, Steven C.R. Williams, Michael Brammer, Vincent P. Giampietro, Joanne Droney, Julia Riley, Paul L. Furlong, Charles H. Knowles, Stafford L. Lightman, Qasim Aziz

Research output: Contribution to journalArticle

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 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. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

LanguageEnglish
Pages2266-2276
Number of pages11
JournalPain
Volume154
Issue number11
Early online date25 May 2013
DOIs
Publication statusPublished - Nov 2013

Fingerprint

Pain
Visceral Pain
Nociceptive Pain
Hydrocortisone
Frontal Lobe
Brain
Anxiety
Magnetic Resonance Imaging
Serotonin Plasma Membrane Transport Proteins
Autonomic Nervous System
Neuroimaging
Chronic Pain
Cluster Analysis
Personality
Healthy Volunteers
Alleles
Genotype
Health
Serum

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Pain. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Farmer, AD, Coen, SJ, Kano, M, Paine, PA, Shwahdi, M, Jafari, J, Kishor, J, Worthen, SF, Rossiter, HE, Kumari, V, Williams, SCR, Brammer, M, Giampietro, VP, Droney, J, Riley, J, Furlong, PL, Knowles, CH, Lightman, SL & Aziz, Q, 'Psychophysiological responses to pain identify reproducible human clusters' Pain. Vol. 154, No. 11 (2014) DOI 10.1016/j.pain.2013.05.016

Funding: Medical Research Council [MGAB1A1R]

Keywords

  • autonomic nervous system
  • hypothalamic-pituitary- adrenal axis
  • personality traits
  • serotonin transporter genotype
  • somatic pain
  • visceral pain

Cite this

Farmer, A. D., Coen, S. J., Kano, M., Paine, P. A., Shwahdi, M., Jafari, J., ... Aziz, Q. (2013). Psychophysiological responses to pain identify reproducible human clusters. Pain, 154(11), 2266-2276. https://doi.org/10.1016/j.pain.2013.05.016
Farmer, Adam D. ; Coen, Steven J. ; Kano, Michiko ; Paine, Peter A. ; Shwahdi, Mustafa ; Jafari, Jafar ; Kishor, Jessin ; Worthen, Sian F. ; Rossiter, Holly E. ; Kumari, Veena ; Williams, Steven C.R. ; Brammer, Michael ; Giampietro, Vincent P. ; Droney, Joanne ; Riley, Julia ; Furlong, Paul L. ; Knowles, Charles H. ; Lightman, Stafford L. ; Aziz, Qasim. / Psychophysiological responses to pain identify reproducible human clusters. In: Pain. 2013 ; Vol. 154, No. 11. pp. 2266-2276.
@article{2703b228846e405995cd26e4eb37b741,
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 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. {\circledC} 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.",
keywords = "autonomic nervous system, hypothalamic-pituitary- adrenal axis, personality traits, serotonin transporter genotype, somatic pain, visceral pain",
author = "Farmer, {Adam D.} and Coen, {Steven J.} and Michiko Kano and Paine, {Peter A.} and Mustafa Shwahdi and Jafar Jafari and Jessin Kishor and Worthen, {Sian F.} and Rossiter, {Holly E.} and Veena Kumari and Williams, {Steven C.R.} and Michael Brammer and Giampietro, {Vincent P.} and Joanne Droney and Julia Riley and Furlong, {Paul L.} and Knowles, {Charles H.} and Lightman, {Stafford L.} and Qasim Aziz",
note = "NOTICE: this is the author’s version of a work that was accepted for publication in Pain. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Farmer, AD, Coen, SJ, Kano, M, Paine, PA, Shwahdi, M, Jafari, J, Kishor, J, Worthen, SF, Rossiter, HE, Kumari, V, Williams, SCR, Brammer, M, Giampietro, VP, Droney, J, Riley, J, Furlong, PL, Knowles, CH, Lightman, SL & Aziz, Q, 'Psychophysiological responses to pain identify reproducible human clusters' Pain. Vol. 154, No. 11 (2014) DOI 10.1016/j.pain.2013.05.016 Funding: Medical Research Council [MGAB1A1R]",
year = "2013",
month = "11",
doi = "10.1016/j.pain.2013.05.016",
language = "English",
volume = "154",
pages = "2266--2276",
journal = "Pain",
issn = "0304-3959",
publisher = "Elsevier",
number = "11",

}

Farmer, AD, Coen, SJ, Kano, M, Paine, PA, Shwahdi, M, Jafari, J, Kishor, J, Worthen, SF, Rossiter, HE, Kumari, V, Williams, SCR, Brammer, M, Giampietro, VP, Droney, J, Riley, J, Furlong, PL, Knowles, CH, Lightman, SL & Aziz, Q 2013, 'Psychophysiological responses to pain identify reproducible human clusters' Pain, vol. 154, no. 11, pp. 2266-2276. https://doi.org/10.1016/j.pain.2013.05.016

Psychophysiological responses to pain identify reproducible human clusters. / Farmer, Adam D.; Coen, Steven J.; Kano, Michiko; Paine, Peter A.; Shwahdi, Mustafa; Jafari, Jafar; Kishor, Jessin; Worthen, Sian F.; Rossiter, Holly E.; Kumari, Veena; Williams, Steven C.R.; Brammer, Michael; Giampietro, Vincent P.; Droney, Joanne; Riley, Julia; Furlong, Paul L.; Knowles, Charles H.; Lightman, Stafford L.; Aziz, Qasim.

In: Pain, Vol. 154, No. 11, 11.2013, p. 2266-2276.

Research output: Contribution to journalArticle

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

N1 - NOTICE: this is the author’s version of a work that was accepted for publication in Pain. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Farmer, AD, Coen, SJ, Kano, M, Paine, PA, Shwahdi, M, Jafari, J, Kishor, J, Worthen, SF, Rossiter, HE, Kumari, V, Williams, SCR, Brammer, M, Giampietro, VP, Droney, J, Riley, J, Furlong, PL, Knowles, CH, Lightman, SL & Aziz, Q, 'Psychophysiological responses to pain identify reproducible human clusters' Pain. Vol. 154, No. 11 (2014) DOI 10.1016/j.pain.2013.05.016 Funding: Medical Research Council [MGAB1A1R]

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. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

KW - autonomic nervous system

KW - hypothalamic-pituitary- adrenal axis

KW - personality traits

KW - serotonin transporter genotype

KW - somatic pain

KW - visceral pain

UR - http://www.scopus.com/inward/record.url?scp=84886290936&partnerID=8YFLogxK

U2 - 10.1016/j.pain.2013.05.016

DO - 10.1016/j.pain.2013.05.016

M3 - Article

VL - 154

SP - 2266

EP - 2276

JO - Pain

T2 - Pain

JF - Pain

SN - 0304-3959

IS - 11

ER -

Farmer AD, Coen SJ, Kano M, Paine PA, Shwahdi M, Jafari J et al. Psychophysiological responses to pain identify reproducible human clusters. Pain. 2013 Nov;154(11):2266-2276. https://doi.org/10.1016/j.pain.2013.05.016