Potential therapeutic value of transient receptor potential channels in male urogenital system

Toktanis, Gamze; Kaya‐Sezginer, Ecem; Yilmaz‐Oral, Didem; Gür, Serap

doi:10.1007/s00424-018-2188-y

Cited by 5 publications

(3 citation statements)

References 121 publications

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“…As mentioned, the neuronal TRPV1 channel may have pathophysiological roles contributing to OAB and pain [101]. The only TRP agonists that have been used clinically for LUT disorders are the toxins capsaicin and RTX, and their application has been extensively reviewed elsewhere [102,103,104,105,106,107]. These toxins are considered to act by eventually desensitizing the TRPV1 channel.…”

Section: Trp Channel Agonists and Antagonistsmentioning

confidence: 99%

TRP Channels as Lower Urinary Tract Sensory Targets

Andersson

2019

Medical Sciences

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Several members of the transient receptor potential (TRP) superfamily, including TRPV1, TRPV2, TRPV4, TRM4, TRPM8 and TRPA1, are expressed in the lower urinary tract (LUT), not only in neuronal fibers innervating the bladder and urethra, but also in the urothelial and muscular layers of the bladder and urethral walls. In the LUT, TRP channels are mainly involved in nociception and mechanosensory transduction. Animal studies have suggested the therapeutic potential of several TRP channels for the treatment of both bladder over- and underactivity and bladder pain disorders,; however translation of this finding to clinical application has been slow and the involvement of these channels in normal human bladder function, and in various pathologic states have not been established. The development of selective TRP channel agonists and antagonists is ongoing and the use of such agents can be expected to offer new and important information concerning both normal physiological functions and possible therapeutic applications.

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Section: Trp Channel Agonists and Antagonistsmentioning

confidence: 99%

TRP Channels as Lower Urinary Tract Sensory Targets

Andersson

2019

Medical Sciences

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“…In addition, TRPA1 has also been shown to play an important role in "dysfunctional pain", a category of pain with an ill-defined cause, where unexplained pain is the main presenting symptom (15). (16). A gain of function mutation in TRPA1 is responsible for familial episodic pain syndrome, and interestingly, antagonists have been shown to inhibit the gain-of-function mutant channel (17).…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammatory gene expression analysis reveals potential novel mediators and treatment targets in interstitial cystitis with Hunner lesions

Werneburg¹,

Keslar²,

Gotwald³

et al. 2021

Transl Androl Urol

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Background: We sought to study differential neuroinflammatory gene expression in men with interstitial cystitis (IC) with Hunner lesions compared with asymptomatic controls using NanoString, which uses barcoded probes to measure hundreds of genes. IC is a heterogenous condition lacking reliable biomarkers, and a subset of patients exhibits Hunner lesions, implicating the bladder as an inflammatory pain generator.Methods: Blood, urine, and bladder biopsies were collected from 6 men with IC and Hunner lesions. 7 asymptomatic controls had blood and urine collected and 2 benign bladder biopsies were obtained from our tissue bank. RNA was isolated and analyzed with NanoString Human Neuroinflammation panel. Gene expression was considered significant if there was a >1.5-fold change and adjusted P value <0.05 compared with controls.Results: Mean patient age was 61.5 years with 8 years median symptom duration. In bladder tissue, while many cytokine and chemokine genes had higher expression as expected (e.g., TNF , CXCL10), other significant genes included TRPA1 (1098-fold increased, expressed in pain sensing neurons) and TNFRSF17 (735-fold, B-cell related). In urine, there was 114-fold increase in S1PR4, which mediates pain via TRPdependent pathways. A patient on cyclosporine had lower inflammatory gene expression levels relative to other IC patients, but no difference in TRPA1.Conclusions: Men with IC and Hunner lesions have a diverse set of neuroinflammatory genes with differential expression compared to controls. We identified genes linked to neuropathic pain through the TRP pathway and this expression was not reduced by cyclosporine. These findings open a new direction for biomarker and therapeutic discovery.

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“…Modulated gene expression in these ontological groups has been reported in the initial response to injury in other peripheral nerves (Bosse et al., 2006; Yao et al., 2012; Yi et al., 2017). Ion channels have a well‐documented role in smooth muscle function and erectile physiology, and changes in the activity of these pathways in cavernosal tissue are likely to contribute to the development of ED (Linton et al., 2012; Thornbury et al., 2019; Toktanis et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

Erectile dysfunction resulting from pelvic surgery is associated with changes in cavernosal gene expression indicative of cavernous nerve injury

2021

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Pelvic surgery, even without direct cavernous nerve injury, carries a high risk of post-operative erectile dysfunction. The present studies were aimed at identifying molecular mechanisms by which pelvic surgery results in erectile dysfunction. As a model of pelvic surgery, male Sprague-Dawley rats underwent pelvic laparotomy, avoiding direct cavernous nerve injury. A second group of animals, serving as a model of direct cavernous nerve injury, underwent bilateral transection of the cavernous nerve. Cavernosometry demonstrated, that even in the absence of direct nerve injury, the pelvic surgery model exhibited significant erectile dysfunction 3 days postoperatively. Gene expression profiling also demonstrated that even in this animal model of nerve-sparing pelvic surgery, the profile of differentially expressed genes in cavernosal tissue was indicative of cavernous nerve injury. In addition, although 6 hr after surgery there were significant changes in circulating cytokine/chemokine levels, an inflammatory response in the major pelvic ganglion, cavernous nerve and cavernosal tissue was only observed 3 days post-surgery. Our results validate a rat model of pelvic surgery exhibiting erectile dysfunction and suggest systemic release of cytokines/chemokines following surgical trauma might mediate a pathological inflammatory response in tissues distal to the site of surgical trauma, indirectly resulting in cavernous nerve injury and erectile dysfunction.

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Potential therapeutic value of transient receptor potential channels in male urogenital system

Cited by 5 publications

References 121 publications

TRP Channels as Lower Urinary Tract Sensory Targets

TRP Channels as Lower Urinary Tract Sensory Targets

Neuroinflammatory gene expression analysis reveals potential novel mediators and treatment targets in interstitial cystitis with Hunner lesions

Erectile dysfunction resulting from pelvic surgery is associated with changes in cavernosal gene expression indicative of cavernous nerve injury

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