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Dopamine Receptor D4 Gene −521C/T Polymorphism Is Associated with Opioid Dependence through Cold‐Pain Responses
Author(s) -
Ho Ada M.C.,
Tang Nelson L.S.,
Cheung Ben K.L.,
Stadlin Alfreda
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1432.054
Subject(s) - opioid , threshold of pain , cold pressor test , pain tolerance , medicine , μ opioid receptor , hyperalgesia , heroin , dopamine , chronic pain , allele , opioid receptor , anesthesia , endocrinology , receptor , pharmacology , gene , nociception , psychiatry , biology , genetics , heart rate , drug , blood pressure
Heroin users exhibit abnormal pain sensitivity called opioid‐induced hyperalgesia that may weaken their determination to abstain. The dopamine receptor D4 gene ( DRD4 ) is associated with heroin dependence; one of its polymorphisms is a C/T variation 521 bp upstream to the gene (−521C/T). We investigated whether this polymorphism was related to opioid dependence through modulation of cold‐pain responses. We recruited 84 heroin‐dependent Chinese male subjects and 168 healthy male Chinese controls. Genotyping was performed by PCR‐RFLP. A significantly higher T allele frequency was observed in the heroin group ( P = 0.041). Of the cohort recruited, 43 current heroin users and 66 controls were further subjected to a cold‐pressor test (CPT) to determine their pain threshold and tolerance. TT controls demonstrated a significantly lower pain threshold than did their CC/CT counterparts ( P = 0.022) and TT opioid users ( P = 0.006). Moreover, CC/CT controls had a significantly higher pain tolerance than TT controls ( P = 0.042) and CC/CT opioid users ( P = 0.010). The data suggest that DRD4 −521C/T plays an important role in opioid dependence through modulating cold‐pain responses. TT individuals might have a higher tendency to use opioids because they experience pain less strongly after chronic opioid use.