Excitatory and inhibitory pain mechanisms during the menstrual cycle in healthy women

Sex differences in pain perception have been clearly documented in the literature during the last decades and it has been shown that women perceived more pain than men. Sex hormones (SHs) are thought to be one of the main mechanisms which explain sex differences in pain. Pain is a dynamic phenomenon involving both excitatory and inhibitory mechanisms. Previous studies have verified the effect of SH on excitatory mechanisms but not on endogenous pain inhibitory mechanisms. The main objective of this study was to establish if pain perception and diffuse noxious inhibitory control (DNIC) vary across the menstrual cycle (MC). Thirty-two healthy women with a regular MC were tested three times across their MC (days 1-3, days 12-14 and days 19-23). Experimental pain consisted of two tonic heat pain stimulations (thermode) separated by a 2-min cold pressor test (CPT) (conditioning stimulus activating DNIC). Pain ratings were measured with a visual analogue scale. Heat pain threshold, pain tolerance and mean pain intensity during both the 2-min thermode test and CPT did not vary throughout the MC. However, we found significantly more pain inhibition (DNIC effectiveness) during the ovulatory phase compared to the menstrual and luteal phases (p=0.05). The main finding of this study is the observation that only inhibitory mechanisms (DNIC analgesia) and not excitatory pain mechanisms vary throughout the MC, where women have greater DNIC in the ovulatory phase. The higher occurrence of pain and lower pain threshold previously reported during the MC could be related to a reduction in endogenous pain control mechanisms.