The role of sex hormones on formalin-induced nociceptive responses

Many chronic pain conditions are more frequent in women than in men. This observation suggests that there is a potential role of sex hormones on pain perception. In the present study, we measured nociceptive responses to the formalin test in normal and gonadectomized male and female rats. The nociceptive responses to formalin injection were divided in four phases: acute (phase I), interphase and late phases (phases II and III). Four groups of rats were tested: (a) males (n = 15), (b) females (n = 16), (c) ovariectomized females (OVX) (n = 15) and (d) castrated males (CAST) (n = 15). Females presented significantly more nociceptive responses than males during phase I, interphase and phase II (P < 0.01). They also presented significantly more nociceptive responses than OVX females during the interphase (P < 0.05). CAST males presented significantly more nociceptive responses during the phases I (P < 0.01), II (P < 0.01) and III (P < 0.05) than the male rats. Finally, the responses of CAST males and OVX females were virtually identical, suggesting that the differences recorded between males and females in the formalin test were related to an activational effect of the sex hormones rather than an organizational effect. In conclusion, these results permit the support of the role of sex hormones on the modulation of pain perception. Interestingly, male and female sex hormones seem to act specifically on the different phases of the formalin test, suggesting some specific roles for sex hormones in different pain conditions.