Exposure to Psychological Stress in Hemopexin Knockout Mice Contributes to Sex-Dependent Increased Pelvic Nociception

Exposure to psychological stress has been previously attributable to the increased pelvic sensitivity in Urologic Chronic Pelvic Pain Syndrome (UCPPS). However, the exact pathway of this relationship is unknown. This study examined the effect of Hemopexin (Hpx) depletion on stress induced-pelvic sensitivity in mice. Hpx is a protein involved in savaging of pro-inflammatory extracellular heme. Adult male and female HPX knockout (KO) mice and wild type (WT) controls were exposed to water-avoidance stress (WAS) and pelvic mechanical sensitivity was assessed using von Frey filaments. Bladder nociception was assessed based on the visceromotor responses (VMR) to balder distentions in females. In vivo electrophysiological recordings were performed in female mice to characterize neuronal activation in response to bladder distensions. The results demonstrate that exposure to WAS increases pelvic sensitivity in male Hpx KO mice but not in Hpx KO females (p<.05) (N=48). However, female Hpx KO mice exposed to WAS demonstrated enhanced VMR compared to the WT females, or Hpx KO females without WAS (N=35). At baseline, Hpx KO mice do not differ in the neuronal activation (N=11). These findings indicate that Hpx depletion and exposure to psychological stress might contribute to enhanced pelvic nociception via different pathways in males and females. On-going studies are examining the spinal neuronal activation following exposure to WAS.