2022 MSC Poster Contest Presentation: Neurexin-3α Has a Role in Varicella Zoster-Associated Orofacial Pain in Male and Proestrus but Not Diestrus Female Rats

Title: Neurexin-3α has a role in varicella zoster-associated orofacial pain in male and proestrus but not diestrus female rats

Presenter: Rebecca Hornung, PhD, postdoctoral research associate, Texas A&M University School of Dentistry, US

Methodology, findings and conclusions of the research
Using a rat model of chronic shingles orofacial pain, we investigated the role of a protein (neurexin-3α) in the brain that acts as a cell adhesion molecule at synapses, in GABA release and motivational pain, in male rats and female rats in diestrus (low plasma estrogen levels) and proestrus (high plasma estrogen levels). Two brain areas that we looked at are the amygdala and parabrachial region. The amygdala has GABA neurons that connect to the parabrachial region and affect pain signals. To target neurexin-3α, we infused a virus that reduces the amount of this protein expressed in the amygdala. To investigate if reducing expression of neurexin-3α also results in a reduction of GABA release, we infused a different virus into a brain region that the amygdala connects with that fluoresces when GABA binds it. In order to see the fluorescent signal, we implanted a fiber optic lens into the same region the GABA sensing virus was infused into. We found that the virus that was infused into the amygdala to reduce expression of neurexin-3α did reduce expression, and the male and proestrus female rats had an increase in their orofacial pain response compared to diestrus rats. In addition, reducing neurexin-3α in the amygdala also resulted in a reduction in GABA release to the parabrachial region. In conclusion, our data is consistent with the idea that neurexin-3α within the amygdala modulates orofacial pain by regulating GABA release to the parabrachial region that then regulates neuronal activity of the ascending pain pathway (pain signals from the site of pain to the brain).

Implications of the research for understanding migraine and/or its comorbidities
Several chronic orofacial pain disorders (migraine, temporomandibular joint disorder (TMD), trigeminal neuralgia) are more prevalent in women. Migraine and TMD pain fluctuate with the menstrual cycle, suggesting modulation of pain by ovarian hormones. Ovarian hormones are known to alter gene expression, which may contribute to the fluctuations in pain throughout the menstrual cycle. In this study, we show that altering expression of a cell adhesion molecule, whose expression is modulated by the rat estrous cycle, within one brain region, modulates activity in another brain region and the animal’s response to orofacial pain. Neurexin-3α protein expression is modulated by the rat estrous cycle and this modulation in expression could also contribute to fluctuations in migraine pain. Targeting neurexin-3α in humans could attenuate migraine pain.