Sensitization of the Trigeminal Sensory System During Different Stages of the Rat Estrous Cycle: Implications for Menstrual Migraine

Abstract

To determine if the sensitization of the trigeminal system changes after dural activation of the trigeminal nerve during different stages of the rat estrous cycle. The specific mechanisms through which ovarian hormones trigger menstrual migraine are currently unknown. Past animal studies have suggested that the response properties of the trigeminal nucleus caudalis (TNC) may change during the different phases of the rat estrous cycle, but none have been performed in an experimental paradigm for migraine headache. Sixty-one cycling female Sprague-Dawley rats were used for these experiments. The stage of the estrous cycle of each animal was identified by examination of the cellular morphology of vaginal lavage. The animals were anesthetized and a 7 mm portion of the skull was removed that was centered over the sagittal sinus. A tungsten electrode was used to record from neurons in the TNC or CI-CIII regions. Only neurons that had both dural and cutaneous receptive fields were used for these experiments. Facial receptive field sizes (RFS) were mapped and neurophysiologic response properties of the TNC/CI-CIII neurons to cutaneous and dural stimuli was ascertained before and after application of capsaicin to the dura. One-way and repeated measure analysis of variance were used to compare changes in RFS and response properties of TNC/CI-CIII neurons from animals during different stages of the rat estrous cycle. When data were analyzed individually for each stage, there was greater enlargement of cutaneous receptive fields and enhanced sensitivity of the trigeminal system to cutaneous stimuli during proestrus as compared to metestrus and diestrus after dural activation with capsaicin (P values <.05). When data were pooled from stages with similar hormonal milieus, the percent change in the response magnitude of TNC neurons to electrical stimulation of the dura was greater and receptive field enlargement was larger from the proestrous/estrous group compared to those from the metestrous/diestrous group after administration of capsaicin (P values <.05). There is enhanced sensitization of the trigeminal system during the later halves of proestrus and estrus, which represent stages of the rat estrous cycle during and immediately following an abrupt decline in ovarian hormones. If similar changes occur during the human menstrual cycle these results could have important implications for menstrual migraine.