TY - JOUR
T1 - Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study
AU - Nielsen, Lecia Møller
AU - Olesen, Anne Estrup
AU - Sato, Hiroe
AU - Christrup, Lona Louring
AU - Drewes, Asbjørn Mohr
N1 - © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental pain model in 40 healthy participants aged 20–65.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.
AB - 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.
KW - Journal Article
U2 - 10.1111/bcpt.12601
DO - 10.1111/bcpt.12601
M3 - Journal article
SN - 1742-7835
VL - 119
SP - 360
EP - 366
JO - Basic & Clinical Pharmacology & Toxicology
JF - Basic & Clinical Pharmacology & Toxicology
IS - 4
ER -