Interstitial cystitis/painful bladder syndrome (IC) is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. IC is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area. In this study, we used a murine neurogenic cystitis model to identify genes participating in the development of pelvic pain. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis (tail base) muscle of female C57BL/6J mice. Mice infected with PRV developed progressive pelvic pain. The sacral spinal cord was harvested on post infection day (PID) 2 and 4, and gene expression was analyzed by microarrays and confirmed by qRT-PCR. On PID 2 the overall expression profile was similar to that of sham-infected sacral spinal cord; by PID 4 there were substantial differences in expression of multiple functional classes of genes, especially inflammation. Analysis of pain signaling pathways at the dorsal horn suggested that Ca2+/Calmodulin-dependent protein kinase II (CaMKII) contributes to neurogenic cystitis pelvic pain. Consistent with this, CaMKIIδ expression exhibited a mast cell-dependent increase in the sacral spinal cord at the mRNA level, and phospho-CaMKII immunoreactivity in the dorsal horn was increased on PID 4 during PRV infection. Finally, intrathecal injection of the CaMKII inhibitor KN-93 attenuated the PRV pain response. These data suggest that CaMKII plays a function role in pelvic pain due to neurogenic cystitis.
- Pelvic pain
- pseudorabies virus
- Copyright © 2012, American Journal of Physiology - Renal Physiology