DRD3 Ser9Gly polymorphism is related to thermal pain perception and modulation in chronic widespread pain patients and healthy controls

J Pain. 2009 Sep;10(9):969-75. doi: 10.1016/j.jpain.2009.03.013. Epub 2009 May 23.


Experimental studies showed that dopamine influences pain perception in healthy volunteers. Dopamine dysfunctions have been linked to the physiopathology of fibromyalgia (FM), which is associated with hyperalgesia and deficient pain inhibition. We sought to investigate the relationships between catecholamine-related polymorphisms [dopamine-D(3) receptor (DRD3) Ser9Gly and catechol-O-methyltransferase (COMT) Val158Met] and thermal pain measures in healthy subjects and FM patients. Seventy-three subjects (37 FM patients and 36 controls) participated in this study. Thermal pain thresholds (TPTs) were measured using a Peltier thermode. Inhibitory systems were elicited using a thermal tonic pain stimulation administered before and after activation of the diffuse noxious inhibitory controls (DNIC) by means of a cold-pressor test. Genetic analyses were performed using polymerase chain reaction. Regression analyses were performed across and within groups. FM was associated with lower TPTs and deficient pain inhibition. DRD3 Ser9Gly polymorphism predicted (1) DNIC efficacy across groups and (2) thermal TPTs in FM patients. COMT Val158Met and thermal pain measures were not related. These preliminary results suggest that the DRD3 Ser9Gly polymorphism influences DNIC efficacy and TPTs and that this latter relationship is present only in FM patients. Two core psychophysical features of FM appear to be significantly influenced by limbic dopamine functioning.

Perspective: This experimental study is the first to relate DNIC and TPTs to a functional polymorphism of limbic dopamine-D3 receptors. As lowered pain thresholds and deficient pain inhibition are 2 core features of fibromyalgia, these preliminary results may help identify a subgroup of FM patients who require closer medical attention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence / genetics
  • Chronic Disease
  • DNA Mutational Analysis
  • Dopamine / metabolism
  • Female
  • Fibromyalgia / genetics
  • Fibromyalgia / metabolism
  • Fibromyalgia / physiopathology
  • Genetic Markers
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Glycine / genetics
  • Humans
  • Hyperalgesia / genetics*
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Limbic System / metabolism
  • Limbic System / physiopathology
  • Male
  • Middle Aged
  • Neural Inhibition / genetics
  • Pain Measurement / methods
  • Pain Threshold / physiology
  • Pain, Intractable / genetics*
  • Pain, Intractable / metabolism
  • Pain, Intractable / physiopathology
  • Polymorphism, Genetic / genetics*
  • Receptors, Dopamine D3 / genetics*
  • Serine / genetics


  • Genetic Markers
  • Receptors, Dopamine D3
  • Serine
  • Glycine
  • Dopamine