The val¹⁵⁸met Polymorphism of Human Catechol-O-Methyltransferase (COMT) Affects Anterior Cingulate Cortex Activation in Response to Painful Laser Stimulation

Abstract

BackgroundPain is a complex experience with sensory, emotional and cognitive aspects. Genetic and environmental factors contribute to pain-related phenotypes such as chronic pain states. Genetic variations in the gene coding for catechol-O-methyltransferase (COMT) have been suggested to affect clinical and experimental pain-related phenotypes including regional μ-opioid system responses to painful stimulation as measured by ligand-PET (positron emission tomography). The functional val158met single nucleotide polymorphism has been most widely studied. However, apart from its impact on pain-induced opioid release the effect of this genetic variation on cerebral pain processing has not been studied with activation measures such as functional magnetic resonance imaging (fMRI), PET or electroencephalography. In the present fMRI study we therefore sought to investigate the impact of the COMT val158met polymorphism on the blood oxygen level-dependent (BOLD) response to painful laser stimulation.Results57 subjects were studied. We found that subjects homozygous for the met158 allele exhibit a higher BOLD response in the anterior cingulate cortex (ACC), foremost in the mid-cingulate cortex, than carriers of the val158 allele.ConclusionThis result is in line with previous studies that reported higher pain sensitivity in homozygous met carriers. It adds to the current literature in suggesting that this behavioral phenotype may be mediated by, or is at least associated with, increased ACC activity. More generally, apart from one report that focused on pain-induced opioid release, this is the first functional neuroimaging study showing an effect of the COMT val158met polymorphism on cerebral pain processing.

Playing nice: a multi-methodological study on the effects of social conformity on memory

“…Second, COMT plays a role in reward and punishment (Tunbridge et al, 2006), making it an intuitive choice for the study of normative pressure, because social disapproval can serve as a powerful aversive stimulus in operant conditioning. Indeed, a previous study demonstrated higher ACC activation in response to painful stimuli for homozygous Met-allele carriers (Mobascher et al, 2010). In addition, an fMRI study by Klucharev et al (2009) found neuroimaging evidence that reinforcement learning signals are relevant for conformist behavior.…”

Alcohol dependence as a chronic pain disorder

“…The met158 allele is associated with higher subjective and brain responses to pain (Mobascher et al, 2010) and suppressed MOR response to pain (Zubieta et al, 2003). Whether the COMT met158 allele influences alcohol dependence remains unclear.…”

Persistent Catechol-O-methyltransferase–dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors

“…14 Furthermore, functional variants in the COMT gene that reduce COMT activity 13,15,16 are associated with increased susceptibility to FM, 17-21 TMD 22 and experimental pain 22,23 as well as impaired response to treatment. 24,25 It is estimated, based on the frequency of allele variation, that nearly two-thirds of patients with chronic pain disorders possess the low-activity COMT variants. 26,27 …”