Abstract
BackgroundThe activation of TRPA1 channel is implicated in hyper-reflexic micturition similar to overactive bladder. In this study, we aimed to investigate the effects of blocking TRPA1 via intrathecal administration of antagonists on the afferent pathways of micturition in rats with cystitis.MethodsThe cystitis was induced by intraperitoneal cyclophosphamide administration. Cystometry was performed in control and cystitis rats, following the intrathecal injection of the TRPA1 antagonists HC-030031 and A-967079. Real-time PCR, agarose gel electrophoresis, western blotting and immunohistochemistry were used to investigate the levels of TRPA1 mRNA or protein in the bladder mucosa and L6-S1 dorsal root ganglia (DRG).ResultsEdema, submucosal hemorrhaging, stiffness and adhesion were noted during removal of the inflamed bladder. The expression of TRPA1 mRNA and protein was higher in the cystitis group in both the mucosa and DRG, but the difference was significant in the DRG (P < 0.05). Intrathecal administration of HC-030031 and A-967079 decreased the micturition reflex in the cystitis group. A 50 μg dose of HC-030031 increased the intercontraction interval (ICI) to 183 % of the no-treatment value (P < 0.05) and decreased the non-voiding contraction (N-VC) to 60 % of control (P < 0.01). Similarly, the treatment with 3 μg A-967079 increased the ICI to 142 % of the control value (P < 0.05) and decreased the N-VC to 77 % of control (P < 0.05). The effects of both antagonists weakened approximately 2 h after injection.ConclusionsThe TRPA1 had a pronounced upregulation in DRG but more slight in mucosa in rat cystitis. The blockade of neuronal activation of TRPA1 by intrathecal administration of antagonists could decrease afferent nerve activities and attenuated detrusor overactivity induced by inflammation.
Highlights
The activation of transient receptor potential channel A1 (TRPA1) channel is implicated in hyper-reflexic micturition similar to overactive bladder
The expression of TRPA1 mRNA was higher in the cystitis group in both the mucosa and dorsal root ganglia (DRG), but the difference was significant in the DRG (P = 0.014)
The present study demonstrates the TRPA1 was expressed in both bladder and DRG (L6-S1) and had a pronounced upregulation in DRG but more slight in mucosa in rat cystitis
Summary
The activation of TRPA1 channel is implicated in hyper-reflexic micturition similar to overactive bladder. The transient receptor potential (TRP) channel A1 is a non-selective ion channel that can cause an influx of cations into the cell when activated It is localized predominantly in small-diameter primary sensory neurons of the dorsal root ganglion and trigeminal ganglion [1,2,3]. Alterations of the TRPA1 channel are known to contribute to mechanical hypersensitivity in primary sensory nerve endings [13]. It is still debated whether the TRPA1 located in neurons become sensitized to nociceptive or mechanical responses in response to visceral inflammation. We hypothesize that the TRPA1 in primary sensory neurons functions as a mechanical or nociceptive receptor and its activation may enhance afferent nerve activities induced by overactive bladder. The blockade of the TRPA1 channel may be a potential therapeutic target for bladder overactivity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
