Abstract
A functional polymorphism (val158met) of the gene coding for Catechol-O-methyltransferase (COM) has been demonstrated to be related to processing of emotional stimuli. Also, this polymorphism has been found to be associated with pain regulation in healthy subjects. Therefore, we investigated a possible influence of this polymorphism on pain processing in healthy persons as well as in subjects with markedly reduced pain sensitivity in the context of Borderline Personality Disorder (BPD). Fifty females (25 patients with BPD and 25 healthy control participants) were included in this study. Genotype had a significant – though moderate - effect on pain sensitivity, but only in healthies. The number of val alleles was correlated with the BOLD response in several pain-processing brain regions, including dorsolateral prefrontal cortex, posterior parietal cortex, lateral globus pallidus, anterior and posterior insula. Within the subgroup of healthy participants, the number of val alleles was positively correlated with the BOLD response in posterior parietal, posterior cingulate, and dorsolateral prefrontal cortex. BPD patients revealed a positive correlation between the number of val alleles and BOLD signal in anterior and posterior insula. Thus, our data show that the val158met polymorphism in the COMT gene contributes significantly to inter-individual differences in neural pain processing: in healthy people, this polymorphism was more related to cognitive aspects of pain processing, whereas BPD patients with reduced pain sensitivity showed an association with activity in brain regions related to affective pain processing.
Highlights
Neural processing of pain has different components besides somatosensory processing [1,2], with affective aspects being processed in anterior insula, anterior cingulate cortex (ACC) and amygdala and cognitive aspects in posterior parietal and dorsolateral prefrontal cortex (DLPFC)
The number of COMT val158 alleles was correlated with the activity of several pain-processing brain regions
We found the number of val alleles to be correlated with cognitive aspects of pain processing in DLPFC and posterior parietal cortex (PPC)
Summary
Neural processing of pain has different components besides somatosensory processing [1,2], with affective aspects being processed in anterior insula, anterior cingulate cortex (ACC) and amygdala and cognitive aspects in posterior parietal and dorsolateral prefrontal cortex (DLPFC). Besides its role in cognitive function, in the prefrontal cortex [4], genetic variations in the gene coding for the enzyme Catechol-O-methyltransferase (COMT) are associated with the processing of emotional stimuli in limbic and prefrontal regions [5,6]. A common functional genetic variation in the COMT gene is the val158met polymorphism with the val variant showing higher enzyme activity than the met variant [7]. The influence of the val158met polymorphism appears to be related to the temporal summation of longer lasting pain stimuli [4]. This polymorphism has been associated with conditions of increased pain [9,10,11]. Increased enzyme activity was associated with higher capacity to activate m-opioid neurotransmission in thalamus, basal ganglia, limbic and paralimbic areas in response to a sustained pain challenge resulting in decreased pain perception [8]
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