COMT val 158 met Genotype Affects µ-Opioid Neurotransmitter Responses to a Pain Stressor

Author:

Zubieta Jon-Kar12,Heitzeg Mary M.1,Smith Yolanda R.3,Bueller Joshua A.1,Xu Ke4,Xu Yanjun1,Koeppe Robert A.2,Stohler Christian S.5,Goldman David4

Affiliation:

1. Department of Psychiatry and Mental Health Research Institute,

2. Department of Radiology,

3. Department of Obstetrics and Gynecology, Medical School, and

4. Laboratory of Neurogenetics, National Institute of Alcohol and Alcoholism, Rockville, MD 20852, USA.

5. Department of Biologic and Materials Sciences, School of Dentistry, The University of Michigan, Ann Arbor, MI 48109–0720, USA.

Abstract

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 met 158 allele of the catechol- O -methyltransferase (COMT) polymorphism ( val 158 met ) 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 val 158 homozygotes. The COMT val 158 met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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