Exposure to Bisphenol A Exacerbates Migraine-Like Behaviors in a Multibehavior Model of Rat Migraine

Migraine is a common and debilitating neurological disorder suffered worldwide. Women experience this condition 3 times more frequently than men, with estrogen strongly implicated to play a role. Bisphenol A (BPA), a highly prevalent xenoestrogen, is known to have estrogenic activity and may have an effect in migraine onset, intensity, and duration through estrogen receptor signaling. It was hypothesized that BPA exposure exacerbates migraine symptoms through estrogen signaling and downstream activation of nociception related pathways. Utilizing a multibehavior model of migraine in ovariectomized female rats, changes in locomotion, light and sound sensitivity, grooming, and acoustic startle were examined. Furthermore, changes in the expression of genes related to estrogen (ERα, GPR30), and nociception (extracellular signal regulated kinase, ERK, sodium gated channel, Nav1.8, and fatty acid amide hydrolase, FAAH) were studied following behavioral experiments. The following results were obtained: BPA treatment significantly exacerbated migraine-like behaviors in rats. Rats exposed to BPA demonstrated decreased locomotion, exacerbated light and sound aversion, altered grooming habits, and enhanced startle reflexes. Furthermore, BPA exposure increased mRNA expression of estrogen receptors, total ERK mRNA and ERK activation, as well as Nav1.8, and FAAH mRNA, indicative of altered estrogen signaling and altered nociception. These results show that BPA, an environmentally pervasive xenoestrogen, exacerbates migraine-like behavior in a rat model and alters expression of estrogen and nociception-related genes.