COMT val158met Genotype Affects µ-Opioid Neurotransmitter Responses to a Pain Stressor

JK Zubieta, MM Heitzeg, YR Smith, JA Bueller, K Xu… - Science, 2003 - science.org
JK Zubieta, MM Heitzeg, YR Smith, JA Bueller, K Xu, Y Xu, RA Koeppe, CS Stohler
Science, 2003science.org
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 μ-opioid system responses to pain compared with heterozygotes. These effects …
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 themet158 allele of the catechol-O-methyltransferase (COMT) polymorphism (val158met) showed diminished regional μ-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 COMTval158met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli.
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