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

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.