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Gender, variation in opioid receptor genes and sensitivity to experimental pain

Hiroe Sato1*, Joanne Droney12, Joy Ross12, Anne Estrup Olesen3, Camilla Staahl3, Trine Andresen3, Ruth Branford12, Julia Riley2, Lars Arendt-Nielsen4 and Asbjørn Mohr Drewes34

Author Affiliations

1 Clinical Genomics group, Imperial College London, London, UK

2 Department of Palliative Medicine, Royal Marsden Hospital, London, UK

3 Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark

4 Center for Sensory-Motor Interactions (SMI), Aalborg University, Aalborg, Denmark

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Molecular Pain 2013, 9:20  doi:10.1186/1744-8069-9-20

Published: 9 April 2013



Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included.


Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain.


This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.

OPRM; OPRK; OPRD; Gender; Pain tolerance thresholds; Opioid receptor genes