Crucial role of TRPC1 and TRPC4 in cystitis-induced neuronal sprouting and bladder overactivity

Purpose During cystitis, increased innervation of the bladder by sensory nerves may contribute to bladder overactivity and pain. The mechanisms whereby cystitis leads to hyperinnervation of the bladder are, however, poorly understood. Since TRP channels have been implicated in the guidance of growth...

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Hauptverfasser: Boudes, Mathieu (VerfasserIn) , Uvin, Pieter (VerfasserIn) , Pinto, Silvia (VerfasserIn) , Freichel, Marc (VerfasserIn) , Birnbaumer, Lutz (VerfasserIn) , Voets, Thomas (VerfasserIn) , Ridder, Dirk De (VerfasserIn) , Vennekens, Rudi (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: July 29, 2013
In: PLOS ONE
Year: 2013, Jahrgang: 8, Heft: 7
ISSN:1932-6203
DOI:10.1371/journal.pone.0069550
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0069550
Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069550
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Verfasserangaben:Mathieu Boudes, Pieter Uvin, Silvia Pinto, Marc Freichel, Lutz Birnbaumer, Thomas Voets, Dirk De Ridder, Rudi Vennekens

MARC

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520 |a Purpose During cystitis, increased innervation of the bladder by sensory nerves may contribute to bladder overactivity and pain. The mechanisms whereby cystitis leads to hyperinnervation of the bladder are, however, poorly understood. Since TRP channels have been implicated in the guidance of growth cones and survival of neurons, we investigated their involvement in the increases in bladder innervation and bladder activity in rodent models of cystitis. Materials and Methods To induce bladder hyperactivity, we chronically injected cyclophosphamide in rats and mice. All experiments were performed a week later. We used quantitative transcriptional analysis and immunohistochemistry to determine TRP channel expression on retrolabelled bladder sensory neurons. To assess bladder function and referred hyperalgesia, urodynamic analysis, detrusor strip contractility and Von Frey filament experiments were done in wild type and knock-out mice. Results Repeated cyclophosphamide injections induce a specific increase in the expression of TRPC1 and TRPC4 in bladder-innervating sensory neurons and the sprouting of sensory fibers in the bladder mucosa. Interestingly, cyclophosphamide-treated Trpc1/c4−/− mice no longer exhibited increased bladder innervations, and, concomitantly, the development of bladder overactivity was diminished in these mice. We did not observe a difference neither in bladder contraction features of double knock-out animals nor in cyclophosphamide-induced referred pain behavior. Conclusions Collectively, our data suggest that TRPC1 and TRPC4 are involved in the sprouting of sensory neurons following bladder cystitis, which leads to overactive bladder disease. 
650 4 |a Bladder 
650 4 |a Cystitis 
650 4 |a Immunohistochemistry techniques 
650 4 |a Nerve fibers 
650 4 |a Neurites 
650 4 |a Neurons 
650 4 |a Sensory neurons 
650 4 |a Transient receptor potential channels 
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700 1 |a Pinto, Silvia  |e VerfasserIn  |4 aut 
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700 1 |a Birnbaumer, Lutz  |e VerfasserIn  |4 aut 
700 1 |a Voets, Thomas  |e VerfasserIn  |4 aut 
700 1 |a Ridder, Dirk De  |e VerfasserIn  |4 aut 
700 1 |a Vennekens, Rudi  |e VerfasserIn  |4 aut 
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