Estrogen receptors localization in the spinal trigeminal nucleus: an immunohistochemical study in humans

There is increasing evidence for estrogenic modulation of neurotransmission within the trigeminal pain pathway. It is also likely that the effects of estrogens may be influenced by the presence and localization of estrogen receptors (ERs) in a given brain area. To date, human data on the localization of ERs in the spinal trigeminal nucleus (STN), a key brain region in craniofacial nociception, are lacking. To ascertain whether ERs are expressed in the human STN, we performed immunohistochemical analysis on medulla oblongata samples taken from eight adult subjects (three men and five women; age range, 23-71 years) who had died from causes unrelated to neurologic or endocrine diseases. Paraffin-embedded sections at the level of the subnucleus caudalis and interpolaris were incubated with anti-estrogen receptor alpha (ERα) and anti-estrogen receptor beta (ERβ) antibodies. ERα immunoreactivity was detected in the nucleus and cytoplasm of neuronal and glial cells in the STN and in the nerve fibers within the spinal trigeminal tract in all eight subjects; ERβ immunoreactivity was observed in the cytoplasm of neuronal cells in five subjects. This study is the first to provide evidence in humans that ER immunoreactivity is detectable on neuronal and glial cells of the STN. The two ER subtypes exhibited different expression patterns, with higher expression levels of ERα than ERβ. The presence of ER-containing cells in the STN suggests that estrogens may directly affect trigeminal neuron excitability in humans.