Individual Differences in Morphine and Butorphanol Analgesia: A Laboratory Pain Study

Objective. Responses to opioid analgesics are highly variable, and the understanding of contributing factors is limited. This laboratory study was designed to examine the contributions of sex and race to inter-individual variability in response to opioids. Design. A randomized, double-blind, mixed design was implemented in the evaluation of analgesic response to a m-opioid agonist and mixed agonist-antagonist, using three well-validated experimental pain assays (thermal, pressure, and ischemic). Subjects. Participants included a total of 142 healthy subjects (76 men/66 women), 119 non-Hispanic whites and 23 African Americans. Intervention. Three sessions of pain testing were completed prior to and following an intravenous administration of morphine (0.08 mg/kg), butorphanol (0.016 mg/kg), and placebo (saline) in counterbalanced order. Outcome Measures. A change score was calculated from the difference between the pre-drug and post-drug values. Three separate change scores (morphine, saline, and butorphanol) were computed for each experimental pain variable. Mixed-model analyses of covariance were performed on analgesic change scores. Results. Significant sex differences emerged for predrug pain measures with minimal differences for race. Sex differences in opioid analgesia were not demonstrated. However, significant race differences and race X drug interactions emerged for thermal, pressure, and ischemic pain measures. The pattern of results generally indicated that for pressure and ischemic pain, African American subjects showed greater analgesic responses to both medications compared with non-Hispanic whites. For thermal pain threshold, butorphanol but not morphine analgesia was greater for African American vs non-Hispanic whites. Conclusions. Findings are among the first to demonstrate race differences in a laboratory study of opioid analgesia.