The multi-issue nature of sex differences in opioid analgesia

Just as the nature of the pain experience can be affected by many factors, both physiologic and psychological, so can the effectiveness of opioid analgesia. Of the many possibilities, three factors are presented in this commentary in response to the preceding Focus article of Miaskowski and Levine. First, two previous studies reporting male-female differences in opioid consumption found such differences to occur only prior to age 60 to 65, at female menopause, suggesting that sex hormonal status should be considered in studies assessing the efficacy of opioid treatment. Second, given that sex and sex hormonal status have been shown to relate to both human and animal physiologic responses to stress and the likelihood that these responses affect nociceptive mechanisms, it is important to further explore these differences in order to optimize pain intervention strategies. Finally, it is encouraged that researchers strive to incorporate chronobiologic and sex hormonal considerations in future animal studies in an effort to more closely model clinical phenomena in exploring biobehavioral responses to stress, pain, and pain-relieving treatment modalities.