Abstract
The aims of this study were to assess the effects of the dopamine agonist apomorphine on experimental pain models in healthy subjects and to explore the possible association between these effects and a common polymorphism within the dopamine transporter gene. Healthy volunteers (n = 105) participated in this randomized double-blind, placebo-controlled, cross-over trial. Heat pain threshold and intensity, cold pain threshold, and the response to tonic cold pain (latency, intensity, and tolerance) were evaluated before and for up to 120 min after the administration of 1.5 mg apomorphine/placebo. A polymorphism (3′-UTR 40-bp VNTR) within the dopamine transporter gene (SLC6A3) was investigated. Apomorphine had an effect only on tolerance to cold pain, which consisted of an initial decrease and a subsequent increase in tolerance. An association was found between the enhancing effect of apomorphine on pain tolerance (120 min after its administration) and the DAT-1 polymorphism. Subjects with two copies of the 10-allele demonstrated significantly greater tolerance prolongation than the 9-allele homozygote carriers and the heterozygote carriers (p = 0.007 and p = 0.003 in comparison to the placebo, respectively). In conclusion, apomorphine administration produced a decrease followed by a genetically associated increase in cold pain tolerance.
Highlights
While the role of norepinephrine, serotonin and opioids in pain perception is well established, the evidence suggesting that dopamine might be involved in these processes is relatively limited
In a recent study conducted in our laboratory on a large cohort of healthy subjects and their parents, a transmission disequilibrium test revealed associations between the dopamine transporter gene (DAT-1), and to a lesser degree between the monoamine oxidase-A gene (MAO-A), and the enhanced ability to tolerate experimental cold pain [6]
The main finding of the present study was that the administration of the nonspecific dopamine agonist apomorphine had an effect on cold pain tolerance, but it did not have any effect on thermal pain threshold or intensity
Summary
While the role of norepinephrine, serotonin and opioids in pain perception is well established, the evidence suggesting that dopamine might be involved in these processes is relatively limited. Painful clinical conditions, such as burning mouth syndrome, fibromyalgia, and restless leg syndrome, are suggested to be linked to abnormalities in dopaminergic neurotransmission [3,4,5]. Additional support for this hypothesis emerges from genetic studies. In a recent study conducted in our laboratory on a large cohort of healthy subjects and their parents, a transmission disequilibrium test revealed associations between the dopamine transporter gene (DAT-1), and to a lesser degree between the monoamine oxidase-A gene (MAO-A), and the enhanced ability to tolerate experimental cold pain [6]. Other reports showing associations between functional polymorphisms in the genes Catechol-O-Methyltransferase (COMT) [7,8], Dopamine Receptor D4 (DRD4) [9,10], and MAO-A [11] and pain phenotypes are in line with our findings, suggesting that a genetic predisposition to dopaminergic activity may be related to pain sensitivity
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