A Search for Sex Differences in Response to Analgesia

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Abstract
IT SEEMS THAT most experts in the field believe that males and females respond differently to painful conditions.1-12 Physiological, psychological, and social factors, as well as cellular, molecular, and genetic factors, may all have an impact on the generation and perception of pain. Under experimental pain conditions, using mechanical or thermal stimuli, females demonstrated a lower pain threshold and a lower tolerance of pain.1-10,12 Sex differences have also been demonstrated in naturally occurring acute and chronic pain situations.13-18 Nevertheless, these sex differences in pain perception are not unequivocal. Some studies have not found a sex-related difference in pain perception using noxious stimuli,19-21 and it has been suggested that there are at present few clear answers on how to apply what we know so far to specific clinical situations.11 Sex differences in analgesic responses have been much less studied. Studies in mice claim to have demonstrated sex and genotype effects on stress-induced analgesia22-25 and sex differences in brain κ-opioid and NMDA receptor activity.26 Very few studies have evaluated sex differences in analgesic response in humans.27-29 In these studies, females experienced greater analgesic efficacy than did males after the administration of κ-opioid receptor agonists in the post–third-molar extraction dental pain model in small groups of subjects. There is also 1 report on sex differences in response to cutaneous anesthesia.30