Sex Differences in Antinociceptive Effects Induced by Gravity Stress in Rats

Abstract

A number of studies have demonstrated that sex differentially affects responses to stress and pain. In this study, sex-related differences in pain responding were investigated in a gravity-induced analgesia model, where the effects of stressful high-gravity loading (1.5G or 2.0G for 10 min) on nociceptive behavior in male and female rats were investigated. In each rat, eight sites (nose, both forepaws, upper and lower back, both hind paws and tail) were selected to apply noxious stimuli using a von Frey-type needle stimulator. The threshold values of the withdrawal responses were measured. In order to confirm the involvement of endogenous opioids in gravity-induced antinociceptive effects, naloxone-HCl (an opioid antagonist) was used. Effective analgesic effects could be induced by strong (2.0G) gravity loading, and clear sex differences were observed. Gravity-induced analgesic effects were more effective in males than in females, indicating that males are more sensitive to stress than females judging from nociceptive modulation. Naloxone-HCl produced a more pronounced suppression of nociceptive behavior in male rats, suggesting that gravity loading may activate endogenous opioids more readily in males than in females.

Stress and opioids: Role of opioids in modulating stress-related behavior and effect of stress on morphine conditioned place preference

“…Other studies have also shown the influence of gender and estrogen on pain-related changes during stress exposure. Stress-induced analgesia is more profound in males than in females suggesting that males are more sensitive to stress than females (Kimoto et al, 2013). It has been reported that kappa opioid receptor-mediated anti-nociceptive and anti-hyperalgesic effects are enhanced by exogenous or endogenous estrogen in the females rats (Lawson et al, 2010).…”