The afferent system and its role in lower urinary tract dysfunction

Daly, Donna; Collins, Valerie M.; Chapple, Christopher R.; Grundy, David

doi:10.1097/mou.0b013e3283476ea2

Cited by 45 publications

(43 citation statements)

References 55 publications

(41 reference statements)

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“…While urothelium has historically been viewed as a simple barrier separating the bladder wall from urine, increasing evidence also suggests that the urothelial cells play a critical role in physiological and pathophysiological processes in the bladder (Daly et al, 2011; Birder and Andersson, 2013; Hill, 2014; Keay et al, 2014; Gonzalez et al, 2014). Specifically, urothelial cells have the capacity to secrete a variety of signaling molecules such as PGE 2 , NGF, nitric oxide, and cytokines in response to various stimuli (Malley and Vizzard, 2002; Wang et al, 2008; Birder and Andersson, 2013; Hill, 2014; Keay et al, 2014; Gonzalez et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Abundance of PCR product was determined semi-quantitatively using a standard curve for each gene. Relative abundance of mRNA in the mucosa was assessed for substances that have been reported to play significant roles in pain and inflammation, including nerve growth factor (NGF), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) (Malley and Vizzard, 2002; Wang et al, 2008; Daly et al, 2011; Birder and Andersson, 2013; Keay et al, 2014; Gonzalez et al, 2014). Expression of each gene was normalized to abundance of mRNA for L19, a constitutively-expressed ribosomal protein in the same sample.…”

Section: Methodsmentioning

confidence: 99%

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Attenuation of Cystitis and Pain Sensation in Mice Lacking Fatty Acid Amide Hydrolase

Wang

Hillard

et al. 2014

J Mol Neurosci

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Endocannabinoids, such as N-arachidonylethanolamine (AEA, also called anandamide), exert potent analgesic and anti-inflammatory effects. Fatty acid amide hydrolase (FAAH) is primarily responsible for degradation of AEA, and deletion of FAAH increases AEA content in various tissues. Since FAAH has been shown to be present in the bladder of various species, we compared bladder function, severity of experimental cystitis, and cystitis-associated referred hyperalgesia in male wild type (WT) and FAAH knock-out (KO) mice. Basal concentrations of AEA were greater, and the severity of cyclophosphamide (CYP)-induced cystitis was reduced in bladders from FAAH KO compared to WT mice. Cystitis-associated increased peripheral sensitivity to mechanical stimuli and enhanced bladder activity (as reflected by increased voiding frequency) were attenuated in FAAH KO compared to WT mice. Further, abundances of mRNA for several pro-inflammatory compounds were increased in bladder mucosa after CYP treatment of WT mice, and this increase was inhibited in FAAH KO mice. These data indicate that endogenous substrates of FAAH, including the cannabinoid AEA, play an inhibitory role in bladder inflammation and subsequent changes in pain perception. Therefore, FAAH could be a therapeutic target to treat clinical symptoms of painful inflammatory bladder diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Attenuation of Cystitis and Pain Sensation in Mice Lacking Fatty Acid Amide Hydrolase

Wang

Hillard

et al. 2014

J Mol Neurosci

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“…Furthermore, atherosclerosis-induced chronic ischemic bladder also decreased constitutive nitric oxide synthase (NOS) (20). Since reports have shown that nitric oxide has both relaxatory and facilitatory effects, as well as having direct effects on the detrusor and modulatory effects via the afferent nerves, it has been suggested that the effect of the nitric oxide on the afferent nerve signaling occurs primarily in an inhibitory fashion (4). The decrease of urinary NOx in the pelvic venous congestion rats examined in the present study might indicate that bladder tissue hypoxia is one of causes of the alterations in the urinary frequency.…”

Section: Discussionmentioning

confidence: 99%

<b>Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous </b><b>congestion </b>

Sugaya¹,

Nishijima²,

Kadekawa³

et al. 2016

Biomed. Res.

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The α1D/A receptor antagonist, naftopidil, inhibits micturition reflex by acting on various different sites. We examined the effects of naftopidil on bladder activity and changes in the induced urinary frequency using female rats with pelvic venous congestion (PC). Twenty-four female rats were divided into sham, PC, and PC/naftopidil groups. After anesthetizing rats in the PC and PC/naftopidil groups, the bilateral common iliac veins and uterine veins were ligated. Rats in the sham and PC groups were fed a standard diet, while rats in the PC/naftopidil group were fed diets containing 0.04% naftopidil. After 4 weeks of treatment, locomotor activity, urinary nitric oxide metabolites (NOx), continuous cystometry, and plasma monoamine measurements were performed. PC rats exhibited a decrease of locomotor activity, a shorter interval between bladder contractions on continuous cystometry, and decreased urinary NOx and plasma serotonin levels than the sham rats. The PC/naftopidil rats exhibited an increase of locomotor activity, a longer interval between bladder contractions, and increased urinary NOx and plasma serotonin levels. Therefore, naftopidil might improve bladder dysfunction induced by pelvic venous congestion due to several actions in the central nervous system and bladder tissue, as well as acting as an α1 blocker to cause pelvic venous dilation.Unilateral or bilateral ovarian vein incompetence can cause pelvic congestion syndrome, which induces chronic pain, irritable bladder, dysfunction of the pelvic organs, or vulval varices and varicose veins in the lower limbs (1, 5, 7). Our previous study demonstrated that chronic prostatitis and stress urinary incontinence were related to the existence of vena cava reflux caused by tricuspid regurgitation (28). When we examined a female case with pelvic congestion syndrome using external iliac venography, we found that pelvic venous congestion occurred with tricuspid regurgitation and without pelvic venous valves (25). Our previous studies have also demonstrated that ligation of the bilateral common iliac veins in male rats or ligation of the bilateral common iliac veins and uterine veins in female rats induced changes in the urinary frequency and low locomotor activity (30). As compared to the intact rats, these surgically altered rats exhibited a bladder blood flow decrease that was about 80% of the flow in the intact bladder. Therefore, pelvic venous congestion may be one of the causes of pelvic ischemia, and might be related to several lower urinary tract symptoms/diseases. When examining hypertension, the relevance of lower urinary tract symptoms and their association with hypertension need to be taken into consideration. Spontaneously hypertensive rats have been shown to have a significantly lower bladder capacity and voiding volume (24), and these rats also exhibit

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“…The urothelium must also communicate information to the underlying sensory nerve fibers to reflect its degree of physical distension, so that both sympathetic and parasympathetic neurons can coordinate their activities to ensure synchronized detrusor smooth muscle contraction and urethral relaxation (17). One of the key neurotransmitters released by the urothelium in response to hydrostatic pressure induced stretch is ATP (21,42,80).…”

Section: Function Of the Urotheliummentioning

confidence: 99%

Defining protein expression in the urothelium: a problem of more than transitional interest

Hill

2011

American Journal of Physiology-Renal Physiology

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Yu W, Hill WG. Defining protein expression in the urothelium: a problem of more than transitional interest. Am J Physiol Renal Physiol 301: F932-F942, 2011. First published August 31, 2011 doi:10.1152/ajprenal.00334.2011.-The transitional epithelium of the bladder, the urothelium, is a challenging tissue to study due to its fragility, complex cellular makeup, stratified composition, and intimate connections to both neural and connective tissue elements. With the increasing focus on the urothelium as a mechanosensory tissue with complex autocrine and paracrine signaling activities, there have arisen a number of unresolved controversies in the urothelial literature regarding whether certain important sensory and signaling proteins are expressed by the urothelium. Prominent examples of this include the transient receptor potential (TRP) family member TRPV1 and the purinergic receptor P2X 3. The problem is more than one of scientific bookkeeping since studies utilizing genetic models (primarily knockout mice) claim additional credibility for urothelial functions when phenotypes are discovered. Furthermore, both of the above-mentioned receptors are important therapeutic targets for various bladder disorders including inflammatory and neuropathic pain. The reasons for the confusion about urothelial expression are manifold, but they likely include low expression levels in some cases, poor specificity of antibodies (sometimes lacking adequate controls), the presence of nonurothelial cells resident within the urothelium, and the fact that the urothelium is particularly prone to aspecific adsorption of antibodies. In this review, we attempt to summarize some of the pitfalls with currently accepted practices in this regard, as well as to describe a set of guidelines which will improve the reliability of conclusions related to urothelial expression. It is hoped that this will be of value to investigators studying the urothelium, to those attempting to interpret conflicts in the literature, and hopefully also those charged with reviewing unpublished work. These recommendations will outline a set of "baseline" and "best practice" guidelines by which both researchers and reviewers will be able to evaluate the evidence presented.

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The afferent system and its role in lower urinary tract dysfunction

Cited by 45 publications

References 55 publications

Attenuation of Cystitis and Pain Sensation in Mice Lacking Fatty Acid Amide Hydrolase

Attenuation of Cystitis and Pain Sensation in Mice Lacking Fatty Acid Amide Hydrolase

<b>Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous </b><b>congestion </b>

Defining protein expression in the urothelium: a problem of more than transitional interest

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