• Arjun Muralidharan and Maree T Smith.
• The University of Queensland, Centre for Integrated Preclinical Drug Development and School of Pharmacy, Steele Building, St Lucia Campus, Brisbane, Queensland, Australia.
• J. Pharm. Pharmacol. 2011 Nov 1;63(11):1387-400.

ObjectivesIn the clinical setting, there is marked intersubject variability in the intensity of pain reported by patients with apparently similar pain states, as well as widely differing analgesic dosing requirements between individuals to produce satisfactory pain relief with tolerable side-effects. Genetic and environmental factors as well as their interaction are implicated, and these are discussed in this review.Key FindingsPioneering work undertaken in mice more than a decade ago, showed a strong genetic contribution to levels of nociception/hypersensitivity as well as levels of antinociception produced by commonly available analgesic agents. To date more than 300 candidate 'pain' genes have been identified as potentially contributing to heritable differences in pain sensitivity and analgesic responsiveness in animals and humans, with this information available in a publicly accessible database http://www.jbldesign.com/jmogil/enter.html. Since then, many genetic association studies have been conducted in humans to investigate the possibility that single nucleotide polymorphisms (SNPs) in an individual gene may explain drug inefficacy or excessive toxicity experienced by a small subset of the whole population who have the rare allele for a particular SNP.SummaryDespite the fact that SNPs in more than 20 genes that affect pain sensitivity or contribute to interindividual variability in responses to analgesic medications have been identified in the human genome, much of the data is conflicting. Apart from deficiencies in the design and conduct of human genetic association studies, recent research from other fields has implicated epigenetic mechanisms that facilitate dynamic gene-environment communication, as a possible explanation.© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

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