Sex Differences in Stress Exacerbated Orofacial Pain in a Rat Model of Temporomandibular Joint Disorder

点击翻译按钮获取中文摘要

Abstract Psychological stress is reported to be a trigger and a result of temporomandibular joint disorder (TMJD) pain, creating a vicious cycle that can exacerbate pain in both men and women. For reasons unclear, TMJD and stress are reported to be more prevalent in women. Preclinical research indicates that subchronic to chronic stress can exacerbate pain in male and female subjects, however the role of stress on occlusive TMJD pain and its underlying mechanisms is unclear. It remains possible that there are undetected sex differences in the effects of stress on trigeminal neurobiology which may contribute to the dimorphic prevalence of TMJD pain. One possible mechanism underlying stress exacerbated TMJD pain may be attributed to dimorphic neural organization and/or function of the trigeminal ganglia (TG) sensory neuron afferents to the parabrachial nucleus (PBN). Additionally, or alternatively, glial cells may play a role in the sexually dimorphic modulation of these circuits during TMJD pain. As microglia in the PBN are activated during both stress and orofacial pain and contribute to inflammation, the role of microglia in stress exacerbated TMJD pain in the PBN of males and females remains unknown. A sexually dimorphic effect of stress on TMJD pain may be one factor underlying the greater prevalence of TMJD in women and filling gaps in our knowledge of the neurobiological mechanisms in the trigeminal system contributing to pain is critical to ultimately improving pain management. Our overarching hypothesis is that sex differences in PBN function contribute to stress exacerbated pain behaviors in a rat model of occlusive TMJD. The goals for this F31 will test our working hypothesis across two specific aims: Specific Aim 1 will determine whether neural activity of PBN neurons receiving sensory input from the TMJ contribute to sex differences in stress exacerbated pain behaviors. Specific Aim 2 will determine whether PBN microglia contribute to sex differences in stress exacerbated pain behaviors in a rat model of occlusive TMJD. Experiments designed under these aims will utilize a combination of behavioral assays, immunohistochemistry, confocal microscopy, flow cytometry, multiplex proteome profiler arrays, and gene sequencing to test the role of the PBN in stress exacerbated orofacial pain. Our preliminary data provide strong support for the hypothesis and our results have the potential to fill a major gap in knowledge on the deleterious effects of stress as a significant trigger and result of TMJD pain.