Comparison of voiding function and nociceptive behavior in two rat models of cystitis induced by cyclophosphamide or acetone

Saitoh, Chikashi; Yokoyama, Hitoshi; Chancellor, Michael B.; Groat, William C. de; Yoshimura, Naoki

doi:10.1002/nau.20777

Cited by 19 publications

(13 citation statements)

References 15 publications

(19 reference statements)

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“…Plasma protein extravasation in the urinary bladder was measured in control and RVS groups by an EB dye leakage technique as described previously (35,60) 24 h after the last stressor exposure. As an additional comparison, 4 h cyclophosphamide (CYP; 150 mg/kg ip)-injected rats were anesthetized (2%), and the femoral vein was exposed.…”

Section: Eb Administration To Assess Plasma Protein Extravasation In mentioning

confidence: 99%

“…After 15 min, the urinary bladder was harvested, transferred to a weigh boat, and placed in an oven at 50°C for 24 h. After 24 h, bladders were removed from the oven and dry weights were collected. Bladders were then placed in tubes with 1 ml formamide and stored at Ϫ4°C in total darkness for 72 h (35,60).…”

Section: Eb Administration To Assess Plasma Protein Extravasation In mentioning

confidence: 99%

“…A disrupted barrier function of the urothelium could underlie increased voiding frequency via activation of the suburothelial nerve plexus (2,5,21). Animal models of cystitis produce dramatic increases in EB levels in the urinary bladder, indicative of a leaky urothelial barrier (35,60). It is well known that EB dye extravasation can be considered an early marker of inflammation.…”

Section: Urothelial Barrier Is Intact After Rvsmentioning

confidence: 99%

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Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

Merrill

Malley

Vizzard

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Merrill L, Malley S, Vizzard MA. Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression. Am J Physiol Regul Integr Comp Physiol 305: R147-R156, 2013. First published May 8, 2013 doi:10.1152/ajpregu.00089.2013.-Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P Յ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P Յ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P Յ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P Յ 0.01) increased at all monofilament forces tested (0.1-4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P Յ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. micturition; stress; nerve growth factor; ELISA; somatic sensitivity STRESS CONTRIBUTES to symptom exacerbation in many disease states, including functional disorders of the urinary bladder such as overactive bladder (OAB) and interstitial cystitis (IC)/ bladder pain syndrome (BPS) (3,38,58,72). Urinary frequency is a common symptom among patients with OAB or IC/BPS, although the end result of frequent voiding may differ [reduce incontinence episodes (OAB) vs. reduce pain with bladder filling (IC/BPS)]. Patients with IC/BPS report symptom worsening during stress, as do patients with other disorders associated with IC/BPS including rheumatoid arthritis, psoriasis, and irritable bowel syndrome (47,72). Symptom worsening during stress may be due, in part, to disruption of the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol, through feedback on the HPA axis, normally acts to attenuate inflammation (47); however, abnormalities in the feedback may cause dysregulation of the inflammatory response. Therefore, patients...

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Section: Eb Administration To Assess Plasma Protein Extravasation In mentioning

confidence: 99%

Section: Eb Administration To Assess Plasma Protein Extravasation In mentioning

confidence: 99%

Section: Urothelial Barrier Is Intact After Rvsmentioning

confidence: 99%

See 1 more Smart Citation

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

Merrill

Malley

Vizzard

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…CYP-induced cystitis is a well-established experimental model of bladder dysfunction due to the accumulation of its metabolite acrolein in the bladder. 2 In rats, an acute intraperitoneal administration of CYP induces signs of pelvic pain, 3 inflammation, 4,5 and alterations to urodynamic parameters. 6,7 So-called ''conventional'' cystometry consists in a continuous bladder infusion via a catheter inserted into the bladder, at defined flow rates, to stimulate micturition reflex.…”

Section: Introductionmentioning

confidence: 99%

Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions

Monjotin

Farrié

Vergnolle

et al. 2016

Neurourology and Urodynamics

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Aims: To establish a new approach to cystometry using telemetry in conscious rats and to use this technique to determine the role of conscious decision making processes with respect to the initiation of voiding in physiological, inflammatory, and painful conditions. Methods: The pressure transducer of a telemetric transmitter was implanted in the dome of the urinary bladder. After a recovery period of at least 1 month, several investigations of urodynamic parameters were performed after diuresis activation by a pulse of furosemide. The model was characterized by tolterodine and mirabegron under physiological conditions and same animals were reused to evaluate the modification of the voiding pattern under bladder inflammation induced by cyclophosphamide. Results: The quality of traces and measurement of parameters recorded telemetrically were comparable to those with conventional cystometry. Furosemide induced a reproducible transient increase of urine production and a series of voids that persisted for 60 min. Tolterodine reduced the amplitude of micturition contractions although mirabegron was devoid of any effect. Seven hours after injection of CYP, voiding frequency increased significantly and the micturition amplitude contraction was not altered. However, the mean volume voided during individual micturitions and the total voided volume decreased. During a second exposure to furosemide 24H after CYP injection, the micturition pattern returned to control, however, the micturition volume was still lower than in control. Conclusion: This telemetric model appears to be as accurate as previously described in conscious conventional cystometry, and allows the repeated evaluation of compounds which may modulate the voiding patterns. Neurourol.

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“…The use of solvent was dispensed with because of concerns about the interaction of the solvent with the urethral mucosa. In animal studies, acetone has been used to induce mucosal damage resulting in a decrease in bladder capacity [5]. It is unknown to which degree local solvent application may facilitate superglue remnant removal from the urethra and whether solvents such as acetone may aggravate the damage to the urethral mucosa.…”

Section: Discussionmentioning

confidence: 99%

Superglue in the Urethra: Surgical Treatment

et al. 2014

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Comparison of voiding function and nociceptive behavior in two rat models of cystitis induced by cyclophosphamide or acetone

Cited by 19 publications

References 15 publications

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions

Superglue in the Urethra: Surgical Treatment

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