Zahari Zalina, Lee Chee Siong, Ibrahim Muslih Abdulkarim, Musa Nurfadhlina, Mohd Yasin Mohd Azhar, Lee Yeong Yeh, Tan Soo Choon, Mohamad Nasir, Ismail Rusli
Department of Pharmacy, Hospital Universiti Sains Malaysia, Kelantan, Malaysia; Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia.
Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia (USM), Kelantan, Malaysia.
Drug Alcohol Depend. 2016 Aug 1;165:143-50. doi: 10.1016/j.drugalcdep.2016.05.028. Epub 2016 Jun 6.
CYP2B6 polymorphisms contribute to inter-individual variations in pharmacokinetics of methadone. Increased pain sensitivity is frequently reported by opioid dependent patients on methadone maintenance therapy (MMT). It is possible, therefore, that genetic polymorphisms in CYP2B6, which affects the metabolism of methadone, influence pain sensitivity among patients on MMT. This study investigated CYP2B6 polymorphisms and pain sensitivity in this group.
The cold pressor pain responses of 148 opioid dependent patients receiving MMT were evaluated using the cold pressor test (CPT). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR)-genotyping.
Of the 148 subjects, 77 (52.0%) were carriers of CYP2B66 allele. CYP2B66 allele carriers had shorter cold pain threshold and pain tolerance times than non-carriers of CYP2B66 allele (21.05s vs 33.69s, p=0.036 and 27.15s vs 44.51s, p=0.020, respectively). Pain intensity scores of the CYP2B66 allele carriers was 67.55, whereas that of the CYP2B6*6 allele non-carriers was 64.86 (p=0.352).
Our study indicates that the CYP2B66 allele is associated with a lower pain threshold and lower pain tolerance among males with opioid dependence on MMT. The CYP2B66 allele may provide a mechanistic explanation for clinical observations of heightened pain sensitivity among opioid dependent patients receiving MMT.
CYP2B6基因多态性导致美沙酮药代动力学存在个体间差异。接受美沙酮维持治疗(MMT)的阿片类药物依赖患者经常报告疼痛敏感性增加。因此,影响美沙酮代谢的CYP2B6基因多态性可能会影响MMT患者的疼痛敏感性。本研究调查了该群体中CYP2B6基因多态性与疼痛敏感性。
采用冷加压试验(CPT)评估148例接受MMT的阿片类药物依赖患者的冷加压疼痛反应。从全血中提取DNA,并进行聚合酶链反应(PCR)基因分型。
在148名受试者中,77名(52.0%)是CYP2B66等位基因携带者。CYP2B66等位基因携带者的冷痛阈值和疼痛耐受时间比非CYP2B66等位基因携带者短(分别为21.05秒对33.69秒,p=0.036;27.15秒对44.51秒,p=0.020)。CYP2B66等位基因携带者的疼痛强度评分为67.55,而CYP2B6*6等位基因非携带者的疼痛强度评分为64.86(p=0.352)。
我们的研究表明,CYP2B66等位基因与接受MMT的阿片类药物依赖男性的较低疼痛阈值和较低疼痛耐受性相关。CYP2B66等位基因可能为接受MMT的阿片类药物依赖患者疼痛敏感性增加的临床观察提供一种机制解释。