Intravesical <i>Escherichia coli</i> lipopolysaccharide stimulates an increase in bladder nerve growth factor

Bjorling, Dale E.; Jacobsen, H.; Blum, J. W.; Shih, Ai; Beckman, Matt; Wang, Z.-Y.; Uehling, David T.

doi:10.1046/j.1464-410x.2001.02138.x

Cited by 34 publications

(29 citation statements)

References 28 publications

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“…Altered NGF content is associated with urinary bladder inflammation and dysfunction in both rodents and humans in which it may underlie neurochemical (10,51,102,112), organizational (101,103), and electrophysiological (108) changes that can affect micturition reflex pathways. In rodents, urinary bladder inflammation induced by noxious chemical or mechanical stimuli increased NGF mRNA and/or protein in the urothelium or detrusor smooth muscle (9,26,78) and caused morphological changes in bladder sensory and motor neurons (26). Urinary bladder inflammation and hypersensitivity induced by CYP (52, 75, 100) or intravesical acrolein (35) also produced changes in NGF or NGF receptor (TrkA and p75 NTR ) expression in micturition reflex pathways.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

Schnegelsberg¹,

Sun

Cain

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

148

275

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Schnegelsberg B, Sun T, Cain G, Bhattacharya A, Nunn PA, Ford AP, Vizzard MA, Cockayne DA. Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function. Am J Physiol Regul Integr Comp Physiol 298: R534 -R547, 2010. First published December 23, 2009; doi:10.1152/ajpregu.00367.2009.-NGF has been suggested to play a role in urinary bladder dysfunction by mediating inflammation, as well as morphological and functional changes, in sensory and sympathetic neurons innervating the urinary bladder. To further explore the role of NGF in bladder sensory function, we generated a transgenic mouse model of chronic NGF overexpression in the bladder using the urothelium-specific uroplakin II (UPII) promoter. NGF mRNA and protein were expressed at higher levels in the bladders of NGF-overexpressing (NGF-OE) transgenic mice compared with wild-type littermate controls from postnatal day 7 through 12-16 wk of age. Overexpression of NGF led to urinary bladder enlargement characterized by marked nerve fiber hyperplasia in the submucosa and detrusor smooth muscle and elevated numbers of tissue mast cells. There was a marked increase in the density of CGRP-and substance P-positive C-fiber sensory afferents, neurofilament 200-positive myelinated sensory afferents, and tyrosine hydroxylase-positive sympathetic nerve fibers in the suburothelial nerve plexus. CGRP-positive ganglia were also present in the urinary bladders of transgenic mice. Transgenic mice had reduced urinary bladder capacity and an increase in the number and amplitude of nonvoiding bladder contractions under baseline conditions in conscious open-voiding cystometry. These changes in urinary bladder function were further associated with an increased referred somatic pelvic hypersensitivity. Thus, chronic urothelial NGF overexpression in transgenic mice leads to neuronal proliferation, focal increases in urinary bladder mast cells, increased urinary bladder reflex activity, and pelvic hypersensitivity. NGF-overexpressing mice may, therefore, provide a useful transgenic model for exploring the role of NGF in urinary bladder dysfunction. nerve growth factor; urothelium; transgenic mouse; bladder hypersensitivity; inflammation; afferent innervation NGF IS A POTENT NEUROTROPHIN that exerts pleiotropic effects in the peripheral and central nervous system. It regulates sensory and sympathetic neuronal development and maintenance (41) and plays a role in painful somatic and visceral inflammation (3,15,32,70,84,85). The effects of NGF are mediated through the TrkA and p75 NTR receptors and are tissue specific. It is well documented that NGF plays an important role in inflammation of the urinary bladder, colon, and lung (21,31,93,100). Although the contribution of NGF to urinary bladder function is unclear, it seems to play a role in urinary bladder hyperreflexia or overactivity (15,16,23,34,40,78,111). NGF administered intrathecally (107), intravesically (23), intramuscularly to the detrusor smooth muscle ...

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Section: Discussionmentioning

confidence: 99%

Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

Schnegelsberg¹,

Sun

Cain

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

148

275

View full text Add to dashboard Cite

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“…In addition, inflammation induced by noxious chemical or mechanical stimulation in the urinary bladder of rodents increases the expression of NGF mRNA as well as protein throughout the bladder, causing morphological changes in both bladder sensory and motor neurons (6,23,39,40). Increases in NGF protein content have also been reported in hypertrophied bladders after spinal cord injury and bladder outlet obstruction, where expression correlates with neuronal hypertrophy and detrusor overactivity (41,43).…”

Section: R896 Social Stress Induction Of Bladder Dysfunctionmentioning

confidence: 99%

Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

Mingin

Peterson

Erickson

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Social stress may play a role in urinary bladder dysfunction in humans, but the underlying mechanisms are unknown. In the present study, we explored changes in bladder function caused by social stress using mouse models of stress and increasing stress. In the stress paradigm, individual submissive FVB mice were exposed to C57BL/6 aggressor mice directly/indirectly for 1 h/day for 2 or 4 wk. Increased stress was induced by continuous, direct/indirect exposure of FVB mice to aggressor mice for 2 wk. Stressed FVB mice exhibited nonvoiding bladder contractions and a decrease in both micturition interval (increased voiding frequency) and bladder capacity compared with control animals. ELISAs demonstrated a significant increase in histamine protein expression with no change in nerve growth factor protein expression in the urinary bladder compared with controls. Unlike stressed mice, mice exposed to an increased stress paradigm exhibited increased bladder capacities and intermicturition intervals (decreased voiding frequency). Both histamine and nerve growth factor protein expression were significantly increased with increased stress compared with control bladders. The change in bladder function from increased voiding frequency to decreased voiding frequency with increased stress intensity suggests that changes in social stress-induced urinary bladder dysfunction are context and duration dependent. In addition, changes in the bladder inflammatory milieu with social stress may be important contributors to changes in urinary bladder function.

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“…(17)(18)(19) NGF, a potent mediator of hyperalgesia associated with inflammation, is upregulated in response to LPS in a mouse cystitis model. (20) We also examined changes in MIF and COX-2 in the prostate in a preliminary attempt to study the possible role of MIF in viscerovisceral interactions. Some of these data have been presented in abstracts.…”

Section: Introduction B Ladder Inflammation Is Associated With Urinarmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Is Upregulated in an Endotoxin-Induced Model of Bladder Inflammation in Rats

Meyer-Siegler

Ordorica²,

Vera³

2004

Journal of Interferon & Cytokine Research

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Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine found in epithelial cells as preformed stores, such that MIF release can activate innate immune responses. Our identification of MIF stores in the urothelium suggests that MIF may function in the bladder's initial response to infectious stimuli, such as lipopolysaccharide (LPS). To test this hypothesis, we observed changes in MIF, cyclooxygenase-2 (COX-2) and c-fos in the bladder, L6-S1 spinal cord, dorsal root ganglion (DRG), and major pelvic ganglion (MPG) and MIF changes in the prostate following intravesical LPS. Intravesical LPS induced bladder edema and leukocyte infiltration, as well as increased MIF protein and mRNA in the bladder and lumbosacral spinal cord. Expression of immediate-early gene c-fos, a transcription factor used as a marker of neuronal activation, increased in the L6-S1 spinal cord and L6-S1 DRG of rats that received LPS. We conclude that significant increases in bladder MIF expression and protein in response to intravesical LPS may represent part of this organ's initial innate immune response. In addition, MIF upregulation may represent a neural response to visceral inflammation. Finally, changes in prostate MIF content after intravesical LPS suggest that MIF may be involved in viscerovisceral interactions associated with chronic pelvic pain syndromes.

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Intravesical Escherichia coli lipopolysaccharide stimulates an increase in bladder nerve growth factor

Cited by 34 publications

References 28 publications

Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

Macrophage Migration Inhibitory Factor Is Upregulated in an Endotoxin-Induced Model of Bladder Inflammation in Rats

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