Sex Differences in Orofacial Sensitivity, Visceral Sensitivity, and Brain Activity in an Animal Model of Stress-induced Pain Hypersensitivity

Abstract

Temporomandibular disorder (TMD) and irritable bowel syndrome (IBS) are two chronic overlapping pain conditions that present with significant comorbidity. Both conditions are more prevalent in women and are exacerbated by stress. While peripheral mechanisms might contribute to pain hypersensitivity for each individual condition, mechanisms underlying the comorbidity are poorly understood, complicating pain management when multiple conditions are involved. We hypothesize that changes in brain function initiated by pre-existing pain combined with stress contributes to development of de novo pain in susceptible individuals. Using an animal model (masseter muscle inflammation followed by stress) that induces de novo Comorbid visceral Pain Hypersensitivity (CPH) in rats, we reported more robust and longer duration CPH in female rats compared to males. The effects of stress alone (Stress-Induced Hypersensitivity, SIH) were examined. The relative percentage of male (9/12) and females (8/14) rats susceptible to stress (increased visceral pain one week post stress) was comparable. The stress resilient rats were excluded from further analysis of visceral pain. Preliminary data from both males and females showed SIH four weeks post stress, resolving by seven weeks in females (ANOVA, females p=.0250); data collection ongoing in males. Additional preliminary data show that stress alone increased orofacial mechanosensitivity in females (p=.0210, n=5), but not males (p=0.4, n=5). In the female cohort, the increased orofacial pain was only apparent in the susceptible females and not the resilient females. Analysis of functional connectivity using functional MRI is underway. Ultimately, changes in functional connectivity in SIH rats will be compared to CPH rats. This study supports our previous work using SIH and CPH groups, suggesting that hypersensitivity in males may resolve faster than in females. Grant support from NIDCR R01 DE029074.