Associations between polymorphisms in dopamine neurotransmitter pathway genes and pain response in healthy humans

Roi Treister, Dorit Pud, Richard P. Ebstein, Efrat Laiba, Edith Gershon, May Haddad, Elon Eisenberg

Research output: Contribution to journalArticlepeer-review


Although evidence shows that several dopamine neurotransmission pathway genes are associated with specific clinical pain syndromes, such as fibromyalgia, chronic headache, and postoperative pain, the exact role of dopamine in pain processing is not fully understood. The aim of this study was to explore the relationship between functional polymorphisms in dopaminergic candidate genes and sensitivity to pain in healthy subjects. Healthy subjects (n = 192; 105 F, 87 M) were exposed to experimental tonic cold pain (1 °C) and phasic heat pain (47 °C) stimuli. DNA samples were obtained from both participants and their parents. The relationships between pain response (intensity in response to heat and cold; threshold and tolerance in response to cold only) and the functional Variable Number of Tandem Repeat (VNTR) polymorphisms of three dopamine-related genes were investigated using a Transmission Disequilibrium Test (TDT). Specifically, 30-bp repeat in the promoter region of the monoamine oxidase-A gene (MAO-A), 40-bp repeat in the 3′-untranslated region of the dopamine transporter gene (DAT-1), and 48-bp repeat in the exon 3 of the dopamine receptor 4 gene (DRD4) were examined. Significant associations between cold pain tolerance and DAT-1 (p = 0.008) and MAO-A (p = 0.024) polymorphisms were found. Specifically, tolerance was shorter for carriers of allele 10 and the rarer allele 11, as compared to homozygous for allele 9, and for carriers of allele 4 as compared to homozygous for allele 3, respectively. These results, together with the known function of the investigated candidate gene polymorphisms, suggest that low dopaminergic activity can be associated with high pain sensitivity and vice versa.

Original languageEnglish
Pages (from-to)187-193
Number of pages7
Issue number1-3
StatePublished - 15 Dec 2009


  • Cold pressor test (CPT)
  • Dopamine transporter
  • Experimental pain
  • Genetics
  • Monoamine oxidase-A

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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