{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:20:31Z","timestamp":1782296431520,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,10,6]],"date-time":"2008-10-06T00:00:00Z","timestamp":1223251200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:p>Heroin users exhibit abnormal pain sensitivity called opioid\u2010induced hyperalgesia that may weaken their determination to abstain. The dopamine receptor D4 gene (<jats:italic>DRD4<\/jats:italic>) is associated with heroin dependence; one of its polymorphisms is a C\/T variation 521 bp upstream to the gene (\u2212521C\/T). We investigated whether this polymorphism was related to opioid dependence through modulation of cold\u2010pain responses. We recruited 84 heroin\u2010dependent Chinese male subjects and 168 healthy male Chinese controls. Genotyping was performed by PCR\u2010RFLP. A significantly higher T allele frequency was observed in the heroin group (<jats:italic>P<\/jats:italic>= 0.041). Of the cohort recruited, 43 current heroin users and 66 controls were further subjected to a cold\u2010pressor test (CPT) to determine their pain threshold and tolerance. TT controls demonstrated a significantly lower pain threshold than did their CC\/CT counterparts (<jats:italic>P<\/jats:italic>= 0.022) and TT opioid users (<jats:italic>P<\/jats:italic>= 0.006). Moreover, CC\/CT controls had a significantly higher pain tolerance than TT controls (<jats:italic>P<\/jats:italic>= 0.042) and CC\/CT opioid users (<jats:italic>P<\/jats:italic>= 0.010). The data suggest that <jats:italic>DRD4<\/jats:italic>\u2212521C\/T plays an important role in opioid dependence through modulating cold\u2010pain responses. TT individuals might have a higher tendency to use opioids because they experience pain less strongly after chronic opioid use.<\/jats:p>","DOI":"10.1196\/annals.1432.054","type":"journal-article","created":{"date-parts":[[2009,8,11]],"date-time":"2009-08-11T11:47:03Z","timestamp":1249991223000},"page":"20-26","source":"Crossref","is-referenced-by-count":23,"title":["Dopamine Receptor D4 Gene \u2212521C\/T Polymorphism Is Associated with Opioid Dependence through Cold\u2010Pain Responses"],"prefix":"10.1196","volume":"1139","author":[{"given":"Ada M.\u2010C.","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson L.\u2010S.","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben K.\u2010L.","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfreda","family":"Stadlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,6]]},"reference":[{"key":"e_1_2_7_2_2","volume-title":"Neuroscience of Psychoactive Substance Use and Dependence","author":"World Health Organization","year":"2004"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-006-0015-1"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1369.010"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crvi.2007.02.017"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-006-9072-9"},{"key":"e_1_2_7_7_2","first-page":"489","article-title":"Pharmacogenetics of alcohol response and alcoholism: the interplay of genes and environmental factors in thresholds for alcoholism","volume":"29","author":"Radel M.","year":"2001","journal-title":"Drug Metab. 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