Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception.
<h4>Background</h4>Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivit...
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doaj-2c93a44f41df42ae84ff1cc03a2c30bc2021-03-04T00:22:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4322110.1371/journal.pone.0043221Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception.Fredrik LindstedtBianka KarshikoffMartin SchallingCaroline Olgart HöglundMartin IngvarMats LekanderEva Kosek<h4>Background</h4>Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities.<h4>Methods</h4>Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C-49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed.<h4>Results</h4>Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged.<h4>Conclusion/significance</h4>To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a 'hypo- to hyperalgesic' response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22952650/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fredrik Lindstedt Bianka Karshikoff Martin Schalling Caroline Olgart Höglund Martin Ingvar Mats Lekander Eva Kosek |
spellingShingle |
Fredrik Lindstedt Bianka Karshikoff Martin Schalling Caroline Olgart Höglund Martin Ingvar Mats Lekander Eva Kosek Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception. PLoS ONE |
author_facet |
Fredrik Lindstedt Bianka Karshikoff Martin Schalling Caroline Olgart Höglund Martin Ingvar Mats Lekander Eva Kosek |
author_sort |
Fredrik Lindstedt |
title |
Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception. |
title_short |
Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception. |
title_full |
Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception. |
title_fullStr |
Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception. |
title_full_unstemmed |
Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain perception. |
title_sort |
serotonin-1a receptor polymorphism (rs6295) associated with thermal pain perception. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
<h4>Background</h4>Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities.<h4>Methods</h4>Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C-49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed.<h4>Results</h4>Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged.<h4>Conclusion/significance</h4>To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a 'hypo- to hyperalgesic' response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22952650/?tool=EBI |
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