Interstitial cystitis: bladder pain and beyond

Ouyang

Neurourology and Urodynamics

et al. 2009

Section: Introductionmentioning

confidence: 99%

Risk factors for poor sleep quality among patients with interstitial cystitis in Taiwan

Ouyang

Neurourology and Urodynamics

et al. 2009

The American Journal of Pathology

“…A multitude of pathogenetic mechanisms have been postulated ranging from neuroinflammatory to autoimmune or possibly infectious or toxic agents, but an inflammatory component is commonly thought to be involved. 4 Epithelial damage has often been invoked: the mucinous layer of the healthy bladder is often compromised in patients with BPS/IC, as well as in some animal models. 5,6 An initiating event (toxin) may lead to increased urothelial permeability, which in turn leads to nerve sensitization and possibly up-regulation of neurotransmitter release (tachykinins, glutamate, calcitonin gene-related peptide).…”

mentioning

confidence: 99%

MicroRNAs May Mediate the Down-Regulation of Neurokinin-1 Receptor in Chronic Bladder Pain Syndrome

Freire

Burkhard

Kessler

et al. 2010

101

Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability , bladder contractility , and inflammation , we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1 , junctional adherins molecule -1 , and occludin were similarly down-regulated , implicating increased urothelial permeability , whereas bradykinin B 1 receptor , cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cellbased models , we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients , the same miRNAs were significantly increased , suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b , miR-500 , miR-328 , and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS , and have relevance for other clinical conditions involving the NK1 receptor. (Am J

Handbook of Experimental Pharmacology

“…Interstitial cystitis or painful bladder syndrome is an idiopathic disease, presenting with bladder pain and urinary frequency or urgency (Kelada and Jones 2007). The bladder pain accompanying interstitial cystitis is regional and chronic and spreads over the lower pelvic and suprapubic area and mimics neuropathic pain (Theoharides et al 2008). In isolated rat urinary bladder, H 2 S stimulates capsaicin-sensitive primary afferent neurons and produces contractile responses (Patacchini et al 2004).…”

Section: Bladder Painmentioning

confidence: 99%

H2S and Pain: A Novel Aspect for Processing of Somatic, Visceral and Neuropathic Pain Signals

Terada

Kawabata

2015

Hydrogen sulfide (H2S) formed by multiple enzymes including cystathionine-γ-lyase (CSE) targets Cav3.2 T-type Ca2+ channels (T-channels) and transient receptor potential ankyrin-1 (TRPA1). Intraplantar and intracolonic administration of H2S donors promotes somatic and visceral pain, respectively, via activation of Cav3.2 and TRPA1 in rats and/or mice. Injection of H2S donors into the plantar tissues, pancreatic duct, colonic lumen, or bladder causes T-channel-dependent excitation of nociceptors, determined as phosphorylation of ERK or expression of Fos in the spinal dorsal horn. Electrophysiological studies demonstrate that exogenous and/or endogenous H2S facilitates membrane currents through T-channels in NG108-15 cells and isolated mouse dorsal root ganglion (DRG) neurons that abundantly express Cav3.2 and also in Cav3.2-transfected HEK293 cells. In mice with cerulein-induced pancreatitis and cyclophosphamide-induced cystitis, visceral pain and/or referred hyperalgesia are inhibited by CSE inhibitors and by pharmacological blockade or genetic silencing of Cav3.2, and CSE protein is upregulated in the pancreas and bladder. In rats with neuropathy induced by L5 spinal nerve cutting or by repeated administration of paclitaxel, an anticancer drug, the neuropathic hyperalgesia is reversed by inhibitors of CSE or T-channels and by silencing of Cav3.2. Upregulation of Cav3.2 protein in DRG is detectable in the former, but not in the latter, neuropathic pain models. Thus, H2S appears to function as a nociceptive messenger by facilitating functions of Cav3.2 and TRPA1, and the enhanced function of the CSE/H2S/Cav3.2 pathway is considered to be involved in the pancreatitis- and cystitis-related pain and in neuropathic pain.