Article

Pain sensitivity and opioid analgesia: A pharmacogenomic twin study

Angst, Martin S.a,*; Phillips, Nicholas G.a; Drover, David R.a; Tingle, Marthaa; Ray, Amritab; Swan, Gary E.c; Lazzeroni, Laura C.b,d; Clark, David J.a,e

Author Information

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

aDepartment of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA

bDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA

cCenter for Health Sciences, SRI International, Menlo Park, CA 94025, USA

dDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA

eDepartment of Anesthesia, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA

*Corresponding author. Address: Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5117, USA. Tel.: +1 650 498 5109; fax: +1 650 725 8052.

E-mail address:[email protected]

Article history: Received 11 September 2011; Received in revised form 12 February 2012; Accepted 17 February 2012.

Pain 153(7):p 1397-1409, July 2012. | DOI: 10.1016/j.pain.2012.02.022

Abstract

TOC Summary 

This twin study demonstrates significant genetic and familial effects for pain sensitivity and opioid analgesia and provides a strong rationale for more detailed genetic studies.

Opioids are the cornerstone medication for the management of moderate to severe pain. Unfortunately, vast inter-individual differences in dose requirements complicate their effective and safe clinical use. Mechanisms underlying such differences are incompletely understood, are likely multifactorial, and include genetic and environmental contributions. While accumulating evidence suggests that variants of several genes account for some of the observed response variance, the relative contribution of these factors remains unknown. This study used a twin paradigm to provide a global estimate of the genetic and environmental contributions to inter-individual differences in pain sensitivity and analgesic opioid effects. Eighty one monozygotic and 31 dizygotic twin pairs successfully underwent a computer-controlled infusion with the μ-opioid agonist alfentanil in a single occasion, randomized, double-blind and placebo-controlled study design. Pain sensitivity and analgesic effects were assessed with experimental heat and cold pressor pain models along with important covariates including demographic factors, depression, anxiety, and sleep quality. Significant heritability was detected for cold pressor pain tolerance and opioid-mediated elevations in heat and cold pressor pain thresholds. Genetic effects accounted for 12–60% of the observed response variance. Significant familial effects accounting for 24–32% of observed variance were detected for heat and cold pressor pain thresholds and opioid-mediated elevation in cold pressor pain tolerance. Significant covariates included age, gender, race, education, and anxiety. Results provide a strong rationale for more detailed molecular genetic studies to elucidate mechanisms underlying inter-individual differences in pain sensitivity and analgesic opioid responses. Such studies will require careful consideration of the studied pain phenotype.

© 2012 Lippincott Williams & Wilkins, Inc.

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