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Using Twins to Understand Opioid Efficacy
SRI studied twins to gain more clinical insight into physiologic response to powerful opioid painkillers.
Opioids are the cornerstone medication for the treatment of moderate to severe pain. However, analgesic opioid requirements and aversive opioid effects, including fatal respiratory depression and addiction, vary widely among patients. The factors underlying the substantial response variance remain largely unknown and need clarification for opioids to be used more effectively in selected patients.
A study of participants from SRI's Twin Research Registry estimated the genetic and environmental contributions to interindividual differences in opioid responses. Evidence of significant inherited traits may justify more detailed and extensive genomic studies.
The enrollment target was 80 identical (monozygotic) and 45 fraternal (dizygotic) twin pairs. They underwent a target-controlled infusion of the opioid alfentanil and saline placebo in sequential but randomized order. In a laboratory setting, well-defined pharmacodynamic endpoints were measured to quantify pain sensitivity, analgesic opioid effects, and aversive opioid effects, including respiratory depression, sedation, and reinforcing affective responses.
Initial results obtained in 159 participants provided evidence for the feasibility and utility of this approach to estimate relevant drug effects related to family traits. Applying the twin paradigm to complex and potentially harmful studies comprehensively characterizing pharmacological response profiles is without much precedent. Methods and first results, including heritability estimates for heat and cold pain sensitivity, should be of interest to investigators considering similar studies.