Behavioral Assessment of Craniofacial Pain: Sex Differences

Algesic stimulation of jaw muscles in lightly anesthetized rats produces nocifensive hindpaw shaking behavior that correlates well with intensity of noxious stimulation and is modulated in a dose-dependent manner to pharmacologic intervention (Ro et al. 2002). Objective: To assess the possibility of sexually dimorphic responses to acute noxious stimulation of the masseter muscle. Methods: Ipsilateral hindpaw shaking behavior was induced by hypertonic saline (HS) injection in the masseter muscle in ovariectomized (OVX) female rats (n=5), OVX females that received a short term estrogen replacement (OVXE, n=6), and weight-matched males (n=4). Animals initially anesthetized with pentobarbital (40mg/kg,i.p.) were allowed to recover until they first showed withdrawal to hindpaw pinch (light anesthesia). Unilateral injections of HS were made in the masseter muscle of all animals. OVXE rats received two daily injections of estrogen (20 mg;s.c.) before masseter injection with HS. Our hypothesis was that OVXE rats would show a greater behavioral response to HS compared to the OVX vehicle injected rats and male rats. Hindpaw shakes were counted in fifteen second bins to determine the time to peak response. The number of hindpaw shakes was plotted over time and the area under the curve was calculated to determine overall magnitude of the response. Observers were blind to hormone status of the OVX animals. Results: Male rats showed a slightly greater peak response but the duration of hindpaw shaking was greater in both OVX and OVXE rats. The magnitude of response in both female groups was significantly greater than that of males (p <.05). However, the magnitude of response was not significantly different between OVX and OVXE rats (p>0.5). Conclusion: These results suggest the existence of a sexually dimorphic response to acute noxious deep tissue stimulation that is independent of reproductive hormones. (Supported by the National Institute of Health DE06027 and DE07334).