The neuroanatomy of sexual dimorphism in opioid analgesia

Abstract

The influence of sex has been neglected in clinical studies on pain and analgesia, with the vast majority of research conducted exclusively in males. However, both preclinical and clinical studies indicate that males and females differ in both the anatomical and physiological composition of central nervous system circuits that are involved in pain processing and analgesia. These differences influence not only the response to noxious stimuli, but also the ability of pharmacological agents to modify this response. Morphine is the most widely prescribed opiate for the alleviation of persistent pain in the clinic; however, it is becoming increasingly clear that morphine is less potent in women compared to men. This review highlights recent research identifying neuroanatomical and physiological dimorphisms underlying sex differences in pain and opioid analgesia, focusing on the endogenous descending pain modulatory circuit.

Manipulation of Neurotransmitter Levels Has Differential Effects on Formalin-Evoked Nociceptive Behavior in Male and Female Mice

“…1,37,39,64 Estrogen can interact with GABA-and NAmediated nociception. Estrogen has also been shown to gate GABAergic tone.…”

Female sex and obesity increase photophobic behavior in mice

“…Sex differences in nocifensive responses to intraplantar capsaicin have also been noted in rats (Lu et al, 2009). Multiple studies have shown differences in endogenous pain inhibition between males and females (Linnman et al, 2012) (Craft et al, 2004; Loyd and Murphy, 2014). Future work will determine to what extent sensitization versus lack of inhibition may be contributing to capsaicin-evoked photophobic behavior in mice.…”

Perils and pitfalls of reporting sex differences

“…Some authors have reported that opioid analgesics are more effective in women than men, some the other way around (reviewed in [63]). Although animal research has suggested that mechanisms of morphine analgesia differs between males and females [74], sex differences in morphine efficacy have been difficult to detect in humans-they may be masked by differences in side effects or pain thresholds [62,63,74].…”