Nielsen Lecia Møller, Olesen Anne Estrup, Sato Hiroe, Christrup Lona Louring, Drewes Asbjørn Mohr
Department of Gastroenterology and Hepatology, Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.
Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Basic Clin Pharmacol Toxicol. 2016 Oct;119(4):360-6. doi: 10.1111/bcpt.12601. Epub 2016 May 2.
The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental pain model in 40 healthy participants aged 20-65. Seventeen different single nucleotide polymorphisms in different genes (OPRM, OPRK, OPRD and COMT) were included in the analysis. Experimental pain tests included thermal skin stimulation, mechanical muscle and bone stimulation and mechanical, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p < 0.015). Additionally, carriers of the C allele (CC/CT) of OPRK rs6473799 reported a 30.4% higher mechanical visceral pain tolerance threshold than non-carriers (TT; p < 0.019). For the other polymorphisms and stimulations, no associations were found (all p > 0.05). In conclusion, COMT rs4680 and OPRK rs6473799 polymorphisms seem to be associated with pain sensitivity. Thus, the findings support a possible genetic influence on pain sensitivity.
基因对有害刺激敏感性（疼痛敏感性）的影响仍存在争议，需要进一步研究。在本研究中，调查了三种阿片受体（OPRM、OPRD和OPRK）基因以及儿茶酚-O-甲基转移酶（COMT）基因的多态性对健康参与者疼痛敏感性的可能影响。儿茶酚-O-甲基转移酶通过改变内源性配体效应来改变μ阿片受体的活性，从而对其产生间接影响。在一个多模式、多组织的实验性疼痛模型中，对40名年龄在20至65岁的健康参与者采集血样进行基因分析。分析中纳入了不同基因（OPRM、OPRK、OPRD和COMT）中的17种不同单核苷酸多态性。实验性疼痛测试包括皮肤热刺激、肌肉和骨骼机械刺激以及机械、电和热内脏刺激。还进行了冷加压试验。40名参与者中有38名可获取DNA。与COMT rs4680A等位基因非携带者相比，携带者报告的骨压疼痛耐受阈值更高（即疼痛较轻），最高可达23.8%（p < 0.015）。此外，OPRK rs6473799的C等位基因（CC/CT）携带者报告的机械性内脏疼痛耐受阈值比非携带者（TT）高30.4%（p < 0.019）。对于其他多态性和刺激，未发现关联（所有p > 0.05）。总之，COMT rs4680和OPRK rs6473799多态性似乎与疼痛敏感性相关。因此，这些发现支持了基因对疼痛敏感性可能存在影响。
