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.

This ongoing study of participants from SRI's Twin Research Registry will estimate the genetic and environmental contributions to interindividual differences in opioid responses. Evidence of significant inherited traits will justify more detailed and extensive genomic studies.

The enrollment target is 80 identical (monozygotic) and 45 fraternal (dizygotic) twin pairs. They undergo a target-controlled infusion of the opioid alfentanil and saline placebo in sequential but randomized order. In a laboratory setting, well-defined pharmacodynamic endpoints are 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.