Furthermore, in a subset (n = 68) of this cohort, the analgesic effect of morphine on experimental pain sensitivity was assessed, which allowed us to examine associations between OPRM1 SNPs and µ-opioid analgesia. Subjects reported ischemic pain threshold, and then at 1 min intervals, subjects rated the intensity and unpleasantness of ischemic arm pain, induced via the submaximal effort tourniquet procedure, before and after the intravenous administration of 0.08 mg/kg of intravenous morphine. The submaximal effort tourniquet procedure was chosen for analgesic assessment because it is among the most sensitive to OPRM1-mediated analgesia (56) when compared with other experimental pain assays. First, the difference in ischemic threshold before and after drug administration was assessed. Then, as described previously (50), summed scores for ratings of pain intensity and unpleasantness across the duration of the tourniquet procedure were computed before and after drug administration. Change scores for summed pain intensity ratings were computed by subtracting the post-drug summed score from the pre-drug summed score, such that larger values indicate a greater reduction in pain following morphine administration, thus greater analgesia. Subjects with
