title: Perception of thermal pain and the thermal grill illusion is associated with polymorphisms in the serotonin transporter gene.
abstract: OBJECTIVE
  The main aim of this study was to assess if the perception of thermal pain thresholds is associated with genetically inferred levels of expression of the 5-HT transporter (5-HTT). Additionally, the perception of the so-called thermal grill illusion (TGI) was assessed. Forty-four healthy individuals (27 females, 17 males) were selected a-priori based on their 5-HTTLPR/rs25531 ('tri-allelic 5-HTTLPR') genotype, with inferred high or low 5-HTT expression. Thresholds for heat- and cold-pain were determined along with the sensory and affective dimensions of the TGI.
  
  
  RESULTS
  Thresholds to heat- and cold-pain correlated strongly (rho  = -0.58, p<0.001). Individuals in the low 5-HTT-expressing group were significantly less sensitive to heat-pain (p = 0.02) and cold-pain (p = 0.03), compared to the high-expressing group. A significant gender-by-genotype interaction also emerged for cold-pain perception (p = 0.02); low 5-HTT-expressing females were less sensitive. The TGI was rated as significantly more unpleasant (affective-motivational dimension) than painful (sensory-discriminatory dimension), (p<0.001). Females in the low 5-HTT expressing group rated the TGI as significantly less unpleasant than high 5-HTT expressing females (p<0.05), with no such differences among men.
  
  
  CONCLUSIONS
  We demonstrate an association between inferred low 5-HTT expression and elevated thresholds to thermal pain in healthy non-depressed individuals. Despite the fact that reduced 5-HTT expression is a risk factor for chronic pain we found it to be related to hypoalgesia for threshold thermal pain. Low 5-HTT expression is, however, also a risk factor for depression where thermal insensitivity is often seen. Our results may thus contribute to a better understanding of the molecular underpinnings of such paradoxical hypoalgesia. The results point to a differential regulation of thermoafferent-information along the neuraxis on the basis of 5-HTT expression and gender. The TGI, suggested to rely on the central integration of thermoafferent-information, may prove a valuable tool in probing the affective-motivational dimension of these putative mechanisms.
authors.affiliation: Osher Center for Integrative Medicine, Stockholm Brain Institute, Department of Clinical Neuroscience Karolinska Institutet, Stockholm, Sweden. fredrik.lindstedt@ki.se
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lindstedt
authors.forename: Tina B
authors.initials: TB
authors.lastname: Lonsdorf
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Eva
authors.initials: E
authors.lastname: Kosek
authors.forename: Martin
authors.initials: M
authors.lastname: Ingvar
mesh_terms: D000328:Adult; D000483:Alleles; D003080:Cold Temperature; D005260:Female; D005838:Genotype; D006801:Humans; D007088:Illusions / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D058748:Pain Perception; D017288:Pain Threshold; D011110:Polymorphism, Genetic; D015203:Reproducibility of Results; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012881:Skin Temperature / Q000235:genetics; D011795:Surveys and Questionnaires; D013696:Temperature; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins