2021 Mitchell Max Awardee
Daisy Cantu
Graduate Student
Texas Woman’s University, Denton, TX
Daisy J. Cantu is originally from Nuevo Laredo, Tamaulipas, Mexico and was adopted into the U.S. at the age of 15. She received her B.S. in Biology from Texas Woman's University (TWU) in 2018. As an undergraduate, Daisy conducted neuroscience research and continued on with this research into graduate school. Daisy earned her M.S. in Biology at TWU in 2020 and is currently a Ph.D. candidate conducting research under the mentorship of Dayna L. Averitt, Ph.D. Her dissertation research focuses on determining the neuroanatomical substrate underlying sex differences in stress-induced exacerbation of orofacial pain. While the vast majority of preclinical research on the effects of stress on orofacial pain are conducted in male rodents, Daisy’s work is focused on characterizing sex differences in the effects of stress on the activity and neurochemistry of trigeminal afferent inputs and the contribution of glial cells in the parabrachial nucleus of female rodents.
Stress Exacerbates Orofacial Pain to a Greater Degree in Female Rats
Cantu, Daisy J., Santos, Natalia, Rodriguez, Erica, Averitt, Dayna L.
Department of Biology, Texas Woman’s University, Denton, Texas
Background: Approximately 20% of the U.S. population suffers from chronic pain, and certain pain conditions in the orofacial region are more prevalent in women. However, there is a limited understanding of why orofacial pain conditions disproportionately affect women. Clinical studies indicate that psychological stress is a contributing factor in the etiology of orofacial pain disorders. Despite this prevalence, the limited research on the effects of stress on orofacial inflammatory pain is reported exclusively in male rodents. A single study in both male and female rats indicates that restraint stress enhances mechanical orofacial allodynia to a greater degree in females during a model of infraorbital neuropathic pain. It remains unclear whether stress-induced exacerbation of orofacial pain occurs in female rodents. Possible mechanisms involved in stress exacerbated orofacial pain may involve the astrocytes, which are known to have a neuroprotective and neurotoxic effect in the brain and spinal cord. Studies have indicated that restraint stress decreases Glial Fibrillary Acid Protein in the brain (GFAP), while other studies have shown that astrocytes significantly increase 1 day after exposure to Complete Freund's Adjuvant (CFA; inflammatory agent) into the masseter muscle. However, the role of astrocytes in stress exacerbated orofacial pain in trigeminal pain pathways, and whether these glial cells are involved in stress exacerbated orofacial pain in females remains unclear. An undetected sexually dimorphic effect of stress on orofacial pain may be one factor underlying the greater prevalence of orofacial pain disorders in women.
Specific aim(s): In this study we examined (1) the role of sub-chronic stress (forced swim test; FST) on inflammatory orofacial mechanical allodynia in female compared to male rats and correlated pain behaviors to (2) plasma corticosterone levels, and (3) astrocyte expression in the trigeminal nucleus caudalis (TNC) and parabrachial nucleus (PBN). We hypothesized that sub-chronic stress evokes greater orofacial pain behaviors and glial activity in the ascending trigeminal pain pathway in female rats.
Results and Significance: Here, we report that CFA (30 μL) injection into the right vibrissal pad evoked significant and comparable mechanical allodynia in both male and female rats. FST evoked a significant and comparable increase in the percentage of time spent immobile. However, females developed greater and longer-lasting orofacial mechanical allodynia one, four, and eight days post-FST. Orofacial pain behaviors returned to normal on day 11, as did corticosterone levels. Also, our preliminary data indicate that inflamed males exposed to the FST express more GFAP in the PBN when compared to sham. On the other hand, female PBN expressed comparable GFAP after exposure to FST or sham conditions, indicating a potential sex dimorphism in astrocyte expression that may be contributing to sex differences during stress exacerbated orofacial pain.
Conclusions: Our data indicate that there are sex differences in the effects of sub-chronic stress on orofacial pain. Understanding the influence of stress on orofacial pain and the role of glial cells is vital to understanding why orofacial pain conditions are more common in women.