Oestrogen receptor-immunoreactive neurons in the trigeminal sensory system of male and cycling female rats

Many common craniofacial pain conditions are more prevalent in women than men and may be related to the phase of the menstrual cycle. Long-term effects of oestrogen in the nervous system are produced by receptor-mediated [oestrogen receptor alpha (ERα) and beta (ERβ) isoforms] mechanisms; however, it is not known if the distribution of ER-positive neurons in the trigeminal system is similar in males and females. Quantitative immunocytochemistry was used to compare the distribution of ERα-labelled neurons in the trigeminal brainstem complex (TBC) and ganglion of male and female rats at different stages of the oestrous cycle. A high density of ERα-labelled neurons was seen in the superficial laminae (I-III) throughout the trigeminal subnucleus caudalis (Vc) and the upper cervical dorsal horn. Counts of ERα-positive neurons in laminae I-III were similar for prooestrous and dioestrous females, while males had fewer cells. The deeper laminae (IV-V) of the Vc and the cervical dorsal horn had few ERα-positive neurons in all groups. At the region surrounding the central canal at caudal levels of the Vc, prooestrous females had more ERα-positive neurons than dioestrous females or males. Few labelled cells were seen rostral to the trigeminal subnucleus interpolaris/caudalis transition region (Vi/Vc) in any group. In the trigeminal ganglion, prooestrous and dioestrous females had a moderate (8-10%) number of nuclear-labelled small or medium-sized neurons, while males had fewer labelled cells (4.5%). Qualitatively, the pattern of staining for ERβ was similar, although weaker, than for ERα in the trigeminal dorsal horn or ganglion. These results were consistent with the hypothesis that oestrogen acts through trigeminal ganglion cells and caudal portions of the Vc to modulate sensory and autonomic aspects of craniofacial pain in a sex-related manner.