Sex differences in thermal nociception and morphine antinociception in rodents depend on genotype

It has been appreciated for some time that the sexes can differ in their se nsitivity to pain and its inhibition. Both the human and rodent literatures remain quite contentious, with many investigators failing to observe sex d ifferences that others document clearly. Recent data from our laboratory ha ve pointed to an interaction between sex and genotype in rodents, such that sex differences are observed in some strains but not others. However, thes e studies employed inbred mouse strains and are thus not directly relevant to existing data. We presently examined whether the observation of statisti cally significant sex differences in nociception and morphine antinocicepti on might depend on the particular outbred rodent population chosen for stud y. Rats of both sexes and three common outbred strains were obtained from t hree suppliers (Long Evans, Simonsen; Sprague Dawley, Harlan; Wistar Kyoto, Taconic) and tested for nociceptive sensitivity on the 49 degrees C tail-w ithdrawal assay, and antinociception following morphine (1-10 mg/kg, i.p.). In further studies, three outbred populations of mice (CD-1, Harlan; Swiss Webster, Harlan; Swiss Webster, Simonsen) were bred in our vivarium for se veral generations and tested for tail-withdrawal sensitivity and morphine a ntinociception (1-20 mg/kg, i.p.). We observed all possible sex comparison patterns for these two traits in different rodent populations: male > femal e, female > male, and no significant difference. In a separate study in whi ch the estrous cycle was tracked in female mice, we found evidence for an i nteraction between genotype and estrous phase relevant to morphine antinoci ception. However, estrous cyclicity did not explain the observed sex differ ences. These data are discussed with respect to the existing sex difference and pain literature, and also as they pertain to future investigations of these phenomena. (C) 2000 Elsevier Science Ltd. All rights reserved.