Characterization of the Expression of BDNF and CGRP and their Regulatory Pathways in Dorsal Root Ganglion during Cystitis.

Interstitial cystitis is a chronic debilitating disease that causes pain and increased frequency of micturition, amongst other symptoms, without any identifiable cause. This disease affects a large number of the population, yet the etiology is still unknown. The present study aimed to characterize BDNF and CGRP—two neuropeptides that have both been proven to play an important role in the transmission of pain as well as in hypersensitivity. The signaling pathways regulating the expression of the two neuropeptides were also examined. Results revealed that BDNF protein expression levels increased in both L1 and L6 DRG following 48 hours post CYP-induced cystitis. CGRP protein expression levels decreased in L1 DRG, but increased in L6 DRG following 48 hours post CYP-induced cystitis. Examination of mRNA levels revealed an increase in the mRNA levels of both BDNF and CGRP in L6 DRG. NGF, a member of the neurotrophin family, mRNA levels also increased following 48 hour CYP-induced cystitis in the urinary bladder. Retrograde analysis revealed NGF possibly retrograde signaled to the DRG to increase BDNF and CGRP expression. Co-localization immunohistochemistry results revealed phospho-Akt co-localized with BDNF, but not with CGRP. Thus NGF retrograde signaling may activate the PI3-K/Akt cascade which may be involved in BDNF expression. CGRP expression may be via another signaling cascade