Article

COMT val(158)met genotype affects mu-opioid neurotransmitter responses to a pain stressor

Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109-0720, USA.
Science (Impact Factor: 31.48). 03/2003; 299(5610):1240-3. DOI: 10.1126/science.1078546
Source: PubMed

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 met158 allele of the catechol-O-methyltransferase (COMT) polymorphism (val158met) showed diminished regional mu-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.

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    • "The COMT VAL158MET SNP appears to be pleiotropic. Although COMT 158MET homozygotes appear to exhibit better executive function, they also exhibit poorer emotional regulation and resiliency in the face of stress compared to carriers of the COMT VAL158 allele (Olsson et al., 2005; Olsson et al., 2007; Pooley, Fineberg, & Harrison, 2007) and stronger response to pain (Zubieta et al., 2003). These effects can be seen in patterns of brain activation. "
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    • "COMT has been implicated in the modulation of pain (Diatchenko et al., 2006). Zubieta et al. (2003) demonstrated that healthy individuals with the COMT Val158Val genotype are pain-resistant. The opposite occurs in people with the Met158Met genotype. "
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    • "Experimentally induced pain has been shown to attenuate sensory and pain-specific affective responses through activation of the opioid system (Zubieta et al., 2001; although see Gilchrist, Allard, & Simone, 1996, regarding cases of secondary hyperalgesia). Disruptions in opioidergic brain activity have also been linked to sadness and depression (Kennedy, Koeppe, Young, & Zubieta, 2006; Prossin et al., 2011; Zubieta et al., 2003), suggesting that physical pain may help regulate emotional pain by activating endogenous opioid release. This is analogous to thrill-seeking behavior (Franken, Zijlstra, & Muris, 2006), which may alleviate emotional numbness through activation of the endogenous opioid system. "
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