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COMT genotypes in pain responses 

COMT genotypes in pain responses
COMT genotypes in pain responses

Matthew Lloyd Hamilton

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date: 28 November 2021

The landmark study discussed in this chapter is ‘COMT val158met genotype affects μ‎-opioid neurotransmitter responses to a pain stressor’, published by Zubieta et al. in 2003. Catechol-O-methyl-transferase (COMT) is a key modulator of dopaminergic and noradrenergic neurotransmission. This study focused on a single nucleotide polymorphism of the COMT gene encoding the substitution of valine (val) by methionine (met) at Codon 158 (val158met), resulting in a three- to fourfold reduction in its activity. Individuals with the val/val genotype have the highest activity of COMT, val/met genotypes have intermediate activity, and met/met genotypes have the lowest activity of COMT. Using a mixture of PET imaging of the binding of μ‎-opioid receptors and correlation with clinical outcomes, this groundbreaking study provided evidence that confirmed their hypothesis and established the COMT val158met SNP as one of the first gene modifications with direct ramifications on human pain.

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