Dopamine Receptor D4 Gene-521C/T Polymorphism Is Associated with Opioid Dependence through Cold-Pain Responses

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 by 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.