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Science 21 February 2003:
Vol. 299. no. 5610, pp. 1240 - 1243
DOI: 10.1126/science.1078546
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Reports

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

Jon-Kar Zubieta,12* Mary M. Heitzeg,1 Yolanda R. Smith,3 Joshua A. Bueller,1 Ke Xu,5 Yanjun Xu,1 Robert A. Koeppe,2 Christian S. Stohler,4 David Goldman5

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 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.

1 Department of Psychiatry and Mental Health Research Institute,
2 Department of Radiology,
3 Department of Obstetrics and Gynecology, Medical School, and
4 Department of Biologic and Materials Sciences, School of Dentistry, The University of Michigan, Ann Arbor, MI 48109-0720, USA.
5 Laboratory of Neurogenetics, National Institute of Alcohol and Alcoholism, Rockville, MD 20852, USA.
*   To whom correspondence should be addressed. E-mail: zubieta{at}umich.edu.

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