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

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 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.