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TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study showing TRPV1 related adaptations in the TRPV4 knockout mouse.

ABSTRACT: The role of transient receptor potential vanilloid subtype 4 (TRPV4) channels in urinary bladder afferent neural pathways was investigated using spinal c-fos measurements in mice. Anesthetized wild type and TRPV4 knockout (-/-) mice underwent noxious bladder distention and treatment with either intravesical instillation with lipopolysaccharide (LPS), or the TRPV1 agonist resiniferatoxin (RTX), vehicle or an intraperitoneal injected TRPV4 antagonist (HC067047). Mice underwent paraformaldehyde perfusion for rapid fixation and L6-S1 spinal cord sections were removed followed by immunohistochemical staining for c-fos. A number of c-fos expressing neurons in the dorsal horns of L6-S1 spinal cord transections were quantified. Groups were compared using univariate ANOVA. Even with the absence of bladder inflammation on H&E, the TRPV4 -/- mice still have a significant twofold higher c-fos expression (n = 39, SD 2) after noxious bladder distention compared to wild type mice (n = 20, SD 3). A twofold increase in c-fos expression was observed after LPS treatment in wild types (n = 42, SD 5), but no increase was seen in TRPV4 -/- mice (n = 42, SD 2). After desensitization of primary afferent C-nerve fibers with RTX, c-fos expression in TRPV4-/- mice decreased significantly (threefold) (n = 12, SD 4). Results imply that TRPV4 channels are important for bladder afferent signaling. TRPV4 -/- mice bladders generate more noxious sensory output, which is predominantly mediated through TRPV1 expressing high threshold nerve fibers. This study reveals TRPV1 related adaptive changes in afferent pathways of the TRPV4 -/- mouse. We propose that this effect is caused by a congenital impairment of low threshold nerves that mediate normal bladder filling sensations.

SUBMITTER: Janssen DA

PROVIDER: S-EPMC5026715 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study showing TRPV1 related adaptations in the TRPV4 knockout mouse.

Janssen Dick A W DA Hoenderop Joost G JG Heesakkers John P F A JP Schalken Jack A JA

Pflugers Archiv : European journal of physiology 20160805 10

The role of transient receptor potential vanilloid subtype 4 (TRPV4) channels in urinary bladder afferent neural pathways was investigated using spinal c-fos measurements in mice. Anesthetized wild type and TRPV4 knockout (-/-) mice underwent noxious bladder distention and treatment with either intravesical instillation with lipopolysaccharide (LPS), or the TRPV1 agonist resiniferatoxin (RTX), vehicle or an intraperitoneal injected TRPV4 antagonist (HC067047). Mice underwent paraformaldehyde per ...[more]

PMID: 27491796

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Project description:BackgroundTraumatic spinal cord injury (SCI) is also a combat-related injury that is increasing in modern warfare. The aim of this work is to inform medical experts regarding the different course of bladder cancer in able-bodied patients compared with SCI patients based on the latest medical scientific knowledge, and to present decision-making aids for the assessment of bladder cancer as a late sequela of traumatic SCI.MethodsA study conducted between January 1998 and December 2019 in the BG Trauma Hospital Hamburg formed the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 40 out of 7396 treated outpatient and inpatient SCI patients. General patient information, latency period, age at initial diagnosis, type of bladder management and survival of SCI patients with bladder cancer were collected and analysed. T category, grading and tumour entity in these patients were compared with those in the general population. Relevant bladder cancer risk factors in SCI patients were analysed. Furthermore, relevant published literature was taken into consideration.ResultsInitial diagnosis of urinary bladder cancer in SCI patients occurs at a mean age of 56.4 years (SD ± 10.7 years), i.e., approximately 20 years earlier as compared with the general population. These bladder cancers are significantly more frequently muscle invasive (i.e., T category ≥ T2) and present a higher grade at initial diagnosis. Furthermore, SCI patients show a significantly higher proportion of the more aggressive squamous cell carcinoma than that of the general population in areas not endemic for the tropical disease schistosomiasis. Consequently, the survival time is extremely unfavourable. A very important finding, for practical reasons is that, in the Hamburg study as well as in the literature, urinary bladder cancer is more frequently observed after 10 years or more of SCI. Based on these findings, a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance.ConclusionsThe results showed that urinary bladder cancer in SCI patients differs considerably from that in able-bodied patients. The presented algorithm is an important aid in everyday clinical practice for assessing the correlation between SCI and bladder cancer.

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TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study showing TRPV1 related adaptations in the TRPV4 knockout mouse.

Publications

TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study showing TRPV1 related adaptations in the TRPV4 knockout mouse.

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