Cyclophosphamide cystitis in rats: involvement of capsaicin-sensitive primary afferents

Maggi, Carlo Alberto; Lecci, Alessandro; Santicioli, Paolo; Bianco, Elena Del; Giuliani, Sandro

doi:10.1016/0165-1838(92)90031-b

Cited by 96 publications

(74 citation statements)

References 21 publications

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“…It is known that NK 1 antagonists (13) and B 2 bradykinin antagonists (19) increase bladder capacity and decrease micturition frequency by acting on the spinal cord in this model. Moreover, CYPinduced detrusor hyperreflexia is abolished when the sensory nerve is functionally impaired by pretreatment of rats with high dose capsaicin (20). Thus, CYPinduced detrusor hyperreflexia is thought to be mediated through stimulation of capsaicin-sensitive afferent neurons.…”

Section: Discussionmentioning

confidence: 89%

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Takagi-Matsumoto

Tsukimi

et al. 2004

J Pharmacol Sci

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Abstract. To clarify the potential usefulness of non-steroidal anti-inflammatory drugs, NSAIDs, for patients with overactive bladder, we examined the effect of NSAIDs on urodynamic parameters in normal and cystitis rats and compared their ulcerogenic activity in the gastrointestinal mucosa. Cystometry was performed after administration of the conventional NSAIDs, aspirin, indomethacin, or ketoprofen. Prostaglandin levels were measured in the bladder of cystitis rats pretreated with NSAIDs. Furthermore, the ulcerogenic responses were examined. NSAIDs increased bladder capacity without any effect on micturition pressure in normal rats in the following rank order of potency: ketoprofen ³ indomethacin ³ aspirin. In cystitis rats, bladder capacity was increased and micturition frequency was decreased. The levels of prostaglandin were significantly increased in cystitis rats. All NSAIDs inhibited the increment of prostaglandin levels at doses equal to that effective in the improvement of bladder functions. When administered intraduodenally, both ketoprofen and indomethacin induced lesions in the gastrointestinal mucosa. However, aspirin had no significant effect. We demonstrate that NSAIDs are effective in animal models of disease, most likely by suppressing by prostaglandin synthesis. Since aspirin, in contrast to ketoprofen or indomethacin, did not cause any gastrointestinal lesions, aspirin might be the NSAIDs treatment of choice for overactive bladder.

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Section: Discussionmentioning

confidence: 89%

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Takagi-Matsumoto

Tsukimi

et al. 2004

J Pharmacol Sci

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“…In contrast, increases in PGD 2 in the urinary bladder were biphasic, occurring with both acute (4 h) and chronic CYP treatment but not acute (48 h) treatment (14). Animal studies have also indicated that CYP treatment (acute treatment) in the rat induces increased frequency of voiding in awake rats and urinary bladder hyperreflexia in anesthetized rats (14,(21)(22)(23)26), and these changes are maintained with acute (48 h) and chronic CYP treatment. Thus CYP treatment represents a noxious, chemical irritation of the urinary bladder that also induces bladder overactivity.…”

Section: Discussionmentioning

confidence: 97%

Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis

LaBerge¹,

Malley²,

Zvarová³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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ticotropin-releasing factor (CRF) is a prominent neuropeptide involved in micturition reflexes, and different roles in these reflexes have been suggested. These studies examined the expression of CRF in the urinary bladder and lumbosacral sacral parasympathetic nucleus (SPN) in response to cyclophosphamide (CYP)-induced cystitis (4 h, 48 h, or chronic) in rats. The expression of CRF receptors, CRF 1 and CRF2, was examined in urinary bladder from control and CYP-treated rats. Urinary bladder and lumbosacral spinal cord were harvested from rats killed by isoflurane (4%) and thoracotomy. CRF protein expression in whole urinary bladders significantly (P Յ 0.01) increased with 48 h or chronic CYP treatment. CRF immunoreactivity (IR) was increased significantly (P Յ 0.01) in the urothelium and SPN after CYP treatment. CRF IR nerve fibers increased in density in the suburothelial plexus and detrusor smooth muscle whole mounts with CYP-induced cystitis. CRF 2 receptor transcript was expressed in the urothelium or detrusor smooth muscle, and CRF2 receptor expression increased in whole bladder with CYP-treatment, whereas no CRF1 receptor transcript was expressed in either urothelium or detrusor. Immunohistochemical studies demonstrated CRF 2 IR in urinary bladder nerve fibers and urothelial cells from control animals, whereas no CRF 1 IR was observed. These studies demonstrated changes in the expression of CRF in urinary bladder and SPN region with CYPinduced cystitis and CRF receptor (CRF 2) expression in nerve fibers and urothelium in control rats. CRF may contribute to urinary bladder overactivity and altered sensory processing with CYP-induced cystitis. inflammation; sacral parasympathetic nucleus; urothelium; enzymelinked immunosorbet assay THE CHEMICALLY (cyclophosphamide, CYP) induced bladder inflammation model is associated with alterations in neurochemical (57, 61), electrophysiological (66), organizational (62), and functional properties (14) of micturition pathways. These changes may be mediated by chemical mediators (e.g., neurotrophins, cytokines, neuropeptides) produced in the bladder, spinal cord, or dorsal root ganglia with cystitis (5, 27, 57, 59, 61).Corticotropin-releasing factor (CRF) is of particular relevance in the rat, since it is present in descending projections from the pontine micturition center or more specifically from Barrington's nucleus to the sacral parasympathetic nucleus (SPN; see Refs. 30,31,49,56). Historically, Barrington's nucleus has been viewed as the supraspinal switching center that regulates storage and elimination of urine (25,33,41). Recent studies have led to the suggestion that Barrington's nucleus may contain neurons that control a broad range of pelvic organ functions (28,29,34,38,55). CRF is prominently expressed in the descending pathway from Barrington's nucleus to the SPN in the lumbosacral spinal cord, and prominent CRF immunoreactivity (IR) is expressed in the SPN of adult rats (37,53,54). Our recent studies have demonstrated an age-dependent upregulation of CRF IR ...

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“…Numerous studies involving a chemically (cyclophosphamide; CYP)-induced bladder inflammation (Cox, 1979;Maggi et al, 1992;Lantéri-Minet et al, 1995;Vizzard, 2000a;Vizzard, 2000d;Zvarova and Vizzard, 2006) model have demonstrated alterations in neurochemical (Vizzard, 2000a;Vizzard, 2000dVizzard, , 2001Zvarova and Vizzard, 2006), electrophysiological (Jennings and Vizzard, 1999;Yoshimura and de Groat, 1999), organizational (Vizzard and Boyle, 1999;Vizzard, 2000b) and functional properties of bladder afferent neurons in dorsal root ganglia (DRG) and in central reflex micturition pathways as well as changes in the urinary bladder (xx). Neurotrophins, including nerve growth factor (NGF) have been implicated in mediating some of these changes.…”

Section: Introductionmentioning

confidence: 99%

Expression of Phosphorylated cAMP Response Element Binding Protein (p-CREB) in Bladder Afferent Pathways in VIP−/− Mice with Cyclophosphamide (CYP)-Induced Cystitis

et al. 2008

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The expression of phosphorylated cAMP response element binding protein (pCREB) in dorsal root ganglia (DRG) with and without CYP-induced cystitis (150 mg/kg, i.p; 48 hr) was determined in VIP −/− and wildtype (WT) mice. p-CREB-immunoreactivity (IR) was determined in bladder (Fastblue) afferent cells. Nerve growth factor (NGF) bladder content was determined by ELISAs. Basal expression of pCREB-IR in DRG of VIP −/− mice was (p ≤ 0.01) greater in L1, L2, L5-S1 DRG compared to WT mice. CYP treatment in WT mice increased (p ≤ 0.05) pCREB-IR in L1, L2, L5-S1 DRG. CYP treatment in VIP −/− mice (p ≤ 0.01) increased (p ≤ 0.01) p-CREB-IR in L6-S1 DRG compared to WT with CYP. In WT mice, bladder afferent cells (20-38%) in DRG expressed pCREB-IR under basal conditions. With CYP, pCREB-IR increased in bladder afferent cells (60-65%; L6-S1 DRG) in WT mice. In VIP −/− mice, bladder afferent cells (12-58%) expressed pCREB-IR under basal conditions and CYP increased pCREB expression (78-84%) in L6-S1 DRG. Urinary bladder NGF expression in VIP −/− mice under basal conditions or after cystitis was significantly greater than WT. Detrusor smooth muscle thickness was significantly increased in VIP −/− mice. Bladder NGF expression may contribute to differences in pCREB expression.

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Cyclophosphamide cystitis in rats: involvement of capsaicin-sensitive primary afferents

Cited by 96 publications

References 21 publications

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Effects of NSAIDs on Bladder Function in Normal and Cystitis Rats: a Comparison Study of Aspirin, Indomethacin, and Ketoprofen

Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis

Expression of Phosphorylated cAMP Response Element Binding Protein (p-CREB) in Bladder Afferent Pathways in VIP−/− Mice with Cyclophosphamide (CYP)-Induced Cystitis

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