PMID- 22952650
OWN - NLM
STAT- MEDLINE
DCOM- 20130219
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 8
DP  - 2012
TI  - Serotonin-1A receptor polymorphism (rs6295) associated with thermal pain 
      perception.
PG  - e43221
LID - 10.1371/journal.pone.0043221 [doi]
LID - e43221
AB  - BACKGROUND: 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. METHODS: 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 degrees C-49 degrees C). Nociceptive-flexion reflex (NFR) thresholds were also assessed. 
      RESULTS: 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. 
      CONCLUSION/SIGNIFICANCE: 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.
FAU - Lindstedt, Fredrik
AU  - Lindstedt F
AD  - Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden. 
      fredrik.lindstedt@ki.se
FAU - Karshikoff, Bianka
AU  - Karshikoff B
FAU - Schalling, Martin
AU  - Schalling M
FAU - Olgart Hoglund, Caroline
AU  - Olgart Hoglund C
FAU - Ingvar, Martin
AU  - Ingvar M
FAU - Lekander, Mats
AU  - Lekander M
FAU - Kosek, Eva
AU  - Kosek E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120831
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Female
MH  - Genotype
MH  - Hot Temperature
MH  - Humans
MH  - Male
MH  - Models, Genetic
MH  - Pain/genetics
MH  - *Pain Perception
MH  - Pain Threshold/physiology
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Single Nucleotide
MH  - Receptor, Serotonin, 5-HT1A/*genetics
MH  - Serotonergic Neurons/metabolism
MH  - Skin Temperature
PMC - PMC3432037
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/09/07 06:00
MHDA- 2013/02/21 06:00
PMCR- 2012/08/31
CRDT- 2012/09/07 06:00
PHST- 2012/02/20 00:00 [received]
PHST- 2012/07/18 00:00 [accepted]
PHST- 2012/09/07 06:00 [entrez]
PHST- 2012/09/07 06:00 [pubmed]
PHST- 2013/02/21 06:00 [medline]
PHST- 2012/08/31 00:00 [pmc-release]
AID - PONE-D-12-05237 [pii]
AID - 10.1371/journal.pone.0043221 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(8):e43221. doi: 10.1371/journal.pone.0043221. Epub 2012 Aug 31.