Increased Severity of Inflammation Correlates with Elevated Expression of TRPV1 Nerve Fibers and Nerve Growth Factor on Interstitial Cystitis/Bladder Pain Syndrome

Liu, Bolong; Yang, Fei; Zhan, Hong; Feng, Zhiying; Zhang, Zhigang; Li, Wen-Biao; Zhou, Xiangfu

doi:10.1159/000355175

Cited by 61 publications

(54 citation statements)

References 28 publications

(50 reference statements)

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“…BoNT/A1 injection for overactive bladder treatment is also associated with a significant decrease of purinergic receptors P2X3 and capsaicin receptors TRPV1, two receptors involved in nociception in the suburothelial nerve fibers (Apostolidis et al, 2005; Liu et al, 2014). These changes may reflect a direct activity of BoNT on the afferent innervation of the bladder and/or a secondary effect on the efferent innervation of the detrusor.…”

Section: Pharmacologymentioning

confidence: 99%

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

et al. 2017

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The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology.

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Section: Pharmacologymentioning

confidence: 99%

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

et al. 2017

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“…Consistently, increased severity of inflammation correlates with upregulation of TRPV1 in bladder nerve fibers of BPS/IC patients (Liu et al. ). These findings suggest that enhanced function or upregulation of TRPV1 in bladder sensory neurons may be responsible for the increased RTX‐evoked nociceptive behaviors in the H 2 O 2 ‐induced rat cystitis model.…”

Section: Discussionmentioning

confidence: 60%

A rat long‐lasting cystitis model induced by intravesical injection of hydrogen peroxide

et al. 2017

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Novel longer lasting inflammatory bladder animal models are needed to better understand the pathophysiology of chronic cystitis. We previously developed a relatively long‐lasting mouse cystitis model by intravesical injection of hydrogen peroxide (H2O2). To further evaluate its pathophysiology, in this study, we established and analyzed a rat cystitis model. Under anesthesia, 1.5% H2O2 solution was introduced transurethrally into the bladder of female rats, and kept for 30 min. The H2O2 injection significantly increased the number of micturition events up to day 14 and decreased urine volume per micturition, with the smallest volumes on day 3, compared with the vehicle‐treated group. Cystometric analysis on day 7 revealed that intercontraction intervals were significantly shortened without affecting the baseline, threshold, or maximum pressures. Intravesical resiniferatoxin‐evoked nociceptive behaviors, such as freezing, were significantly enhanced on days 7 and 14. Furthermore, histopathology revealed hemorrhage, edema, infiltration of neutrophils into the lamina propria, and urothelial denudation in the early phase (day 1). These damages were gradually repaired, while hyperplasia of the urothelium, vascularization, increases in fibroblast counts, and infiltration of mast cells and eosinophils were observed through the later phase (days 7 and 14). These results suggest that intravesical H2O2 injection induces relatively long‐lasting cystitis with enhanced bladder activity and pain sensation in rats. This approach thus provides a novel rat long‐lasting cystitis model that allows us to analyze detailed symptoms and pathophysiology of H2O2‐induced cystitis model than the mouse model and may be used to investigate the pathophysiology and treatment of chronic bladder hypersensitive disorders, such as bladder pain syndrome/interstitial cystitis.

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“…We found that BPS/IC was significantly associated with previous statin use, and the Although there is no consensus on a mechanism to explain the underlying cause of BPS/IC, several pathophysiologic mechanisms have been proposed, including epithelial dysfunction, mast cell activation, and neurogenic inflammation [19][20][21] . In addition, many recent studies reported that a higher level of cell apoptosis in the urothelium was associated with inflammation in patients with BPS/IC [22][23][24][25] .…”

Section: Discussionmentioning

confidence: 99%

Statin Use Is Associated with Bladder Pain Syndrome/Interstitial Cystitis: A Population-Based Case-Control Study

Huang

Chung

Lin³

et al. 2015

Urol Int

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Introduction: Statin may induce epithelial dysfunction of the bladder urothelium. Epithelial dysfunction was proposed as one of the major potential etiologies for bladder pain syndrome/interstitial cystitis (BPS/IC). In this study, we examined the association between statin use and BPS/IC using a population-based study. Subjects and Methods: This case-control study used the Taiwan Longitudinal Health Insurance Database. In total, 815 female subjects with BPS/IC and 4075 randomly selected female controls were included. We used a conditional logistic regression to compute the odds ratio (OR) for having previously used statins between cases and controls. Results: A conditional logistic regression analysis showed that the OR of prior statin users for cases was 1.52 (95% confidence interval (CI): 1.19-1.94) compared to controls after adjusting for diabetes, hypertension, coronary heart disease, obesity, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma. Furthermore, adjusted ORs of regular and irregular statin use for cases were 1.58 (95% CI: 1.20-2.08) and 1.53 (95% CI: 1.02-2.31), respectively, compared to controls. Conclusion: We concluded that there was an association between statin use and BPS/IC.

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Increased Severity of Inflammation Correlates with Elevated Expression of TRPV1 Nerve Fibers and Nerve Growth Factor on Interstitial Cystitis/Bladder Pain Syndrome

Cited by 61 publications

References 28 publications

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

A rat long‐lasting cystitis model induced by intravesical injection of hydrogen peroxide

Statin Use Is Associated with Bladder Pain Syndrome/Interstitial Cystitis: A Population-Based Case-Control Study

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