COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor

Science. 2003 Feb 21;299(5610):1240-3. doi: 10.1126/science.1078546.


Responses to pain and other stressors are regulated by interactions between multiple brain areas and neurochemical systems. We examined the influence of a common functional genetic polymorphism affecting the metabolism of catecholamines on the modulation of responses to sustained pain in humans. Individuals homozygous for the met158 allele of the catechol-O-methyltransferase (COMT) polymorphism (val158met) showed diminished regional mu-opioid system responses to pain compared with heterozygotes. These effects were accompanied by higher sensory and affective ratings of pain and a more negative internal affective state. Opposite effects were observed in val158 homozygotes. The COMT val158met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Affect
  • Amino Acid Substitution
  • Analysis of Variance
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain Mapping
  • Catechol O-Methyltransferase / chemistry
  • Catechol O-Methyltransferase / genetics*
  • Catechol O-Methyltransferase / metabolism
  • Cerebellum / diagnostic imaging
  • Cerebellum / metabolism
  • Female
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways
  • Pain*
  • Polymorphism, Genetic
  • Radionuclide Imaging
  • Receptors, Opioid, mu / metabolism*
  • Synaptic Transmission
  • Thalamus / metabolism


  • Receptors, Opioid, mu
  • Catechol O-Methyltransferase