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Genetic Influences of OPRM 1 , OPRD 1 and COMT on Morphine Analgesia in a Multi‐Modal, Multi‐Tissue Human Experimental Pain Model
Author(s) -
Nielsen Lecia M.,
Christrup Lona L.,
Sato Hiroe,
Drewes Asbjørn M.,
Olesen Anne E.
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12757
Subject(s) - rs4680 , morphine , catechol o methyl transferase , crossover study , medicine , anesthesia , stimulation , placebo , cold pressor test , pharmacology , opioid , hyperalgesia , genotype , receptor , nociception , biology , gene , blood pressure , pathology , genetics , heart rate , alternative medicine
Human studies on experimentally induced pain are of value to elucidate the genetic influence on morphine analgesia under controlled conditions. The aim of this study was to investigate whether genetic variants of mu‐, kappa‐ and delta‐opioid receptor genes ( OPRM 1 , OPRK 1 and OPRD 1 ) and catechol‐ O ‐methyltransferase gene ( COMT ) are associated with the morphine analgesia. The study was a randomized, double‐blind, two‐way, crossover, single‐dose study conducted in 40 healthy participants, where morphine was compared with placebo. Pain was induced by contact heat, muscle pressure, bone pressure, rectal stimulations (mechanical, electrical and thermal) and cold pressor test (immersion of the hand into ice water). Sixteen genetic polymorphisms of four candidate genes were explored. Variability in morphine analgesia to contact heat stimulation was associated with COMT rs4680 ( p = 0.04), and rectal thermal stimulation was associated with OPRM 1 rs9479757 ( p = 0.03). Moreover, in males, variability in morphine analgesia to rectal thermal stimulation was associated with OPRD 1 polymorphisms: rs2234918 ( p = 0.01) and rs533123 ( p = 0.046). The study was explorative and hypothesis‐generating due to the relatively small study size. However, results suggest that genetic variants in the COMT and OPRM 1 irrespective of gender, and OPRD 1 in males may contribute to the variability in morphine analgesia in experimental pain models.