The pain-sensitivity score was calculated as follows. Each participant in the analyzed cohort was quantified for responsiveness to a number of noxious modalities (thermal, mechanical and ischemic) applied to various anatomical sites (46,47). Because opioids such as morphine modify the perceptual responses to all of the assessed noxious modalities (48–51), we derived a unitary quantitative measure of pain sensitivity for the quantitative analyses. To accomplish this, each of 16 measures of pain sensitivity was normalized to a mean of zero and standard deviation of one, producing a unit normal deviate (z-score) for each test procedure. A sum of these 16 scores produced a normalized single score of pain sensitivity (summary z-score) for each individual (see Supplementary Material for details). We thus hypothesized that population variations in the constructed global measures of pain sensitivity would be associated with functional genetic polymorphisms in OPRM1.
