The role of estrogen in trigeminal hypersensitivity

Abstract

Migraine and temporomandibular disease are three times more common in women than in men and temporally related to the hormonal fluctuations of the menstrual cycle. We examined mechanical sensitivity of the temporomandibular joint in ovariectomized rats in a 2x2 model of TMJ inflammation and estrogen replacement. Mechanical sensitivity of the TMJ was increased by administration of Complete Freund’s Adjuvant (CFA) and estrogen, with a synergistic effect achieved from concurrent administration of CFA and estrogen. Because the MAP kinase Extracellular-signal regulated kinase (ERK) has been implicated in hypersensitivity of neurons following inflammation, ERK activation was examined in trigeminal ganglia of rats from the 2x2 model using immunohistochemistry. The number of cells expressing activated ERK in each group paralleled the mechanical sensitivity data. Because estrogen has been shown to activate ERK, we examined the distribution of Estrogen Receptor α and the rapid signaling estrogen receptor GPR30 in trigeminal ganglia from the same animals. Both receptors were widely distributed in trigeminal neurons, and ERα was downregulated by estrogen replacement.