Search

Visceral inflammation and pain associated with chemical cystitis produce increased sensitivity to noxious stimuli in the sacral dermatomes. We determined whether a similar sensitization occurs in response to bacterial cystitis.Bacterial cystitis was induced by intravesical instillation of Escherichia coli 1677 in female C57BL/6N and C3H/OuJ mice (Jackson Laboratories, Bar Harbor, Maine). C3H/HeJ mice (Jackson Laboratories) served as a control because C3H/HeJ mice lack functional toll-like receptor 4, which is an essential component of cellular recognition of bacterial lipopolysaccharide. Hind paw sensitivity to thermal stimulus was quantitatively determined 1, 2, 7 and 14 days after infection.Intravesical instillation of E. coli produced infection in all strains of mice. Infection persisted in all C3H/OuJ and C3H/HeJ mice but it spontaneously cleared in some C57BL/6N mice. Increased sensitivity to thermal stimuli was observed in C57BL/6N and C3H/OuJ mice starting 1 to 2 days after E. coli instillation and it was still present 14 days after instillation. Increased sensitivity to thermal stimuli did not occur in C3H/HeJ mice.E. coli induced cystitis produced increased sensitivity to peripheral thermal stimuli in mice with competent toll-like receptor 4.

Aims Lidocaine produces analgesia by inhibiting excitation of nerve endings or blocking impulse conduction in peripheral nerves. This study was performed to determine whether intrathecal or intravesical administration of lidocaine prior, or subsequent, to induction of chemical cystitis in rats would block referred mechanical hyperalgesia. Methods Intrathecal or intravesical lidocaine was administered 15 (intrathecal) or 30 (intravesical) min before intravesical instillation of saline or 1 mM acrolein (400 µl) or 4 hr after saline or acrolein instillation in female Wistar rats. Mechanical sensitivity of hind paws was determined at 24 hr prior to any treatment (baseline) and, 4, 24, and 48 hr after intravesical instillation of acrolein or saline. Also, nerve growth factor (NGF) content was measured in bladder and dorsal root ganglia (DRG). Results Pre-treatment with intrathecal or intravesical lidocaine attenuated acrolein-induced referred mechanical hyperalgesia of the hind paws. Lidocaine administered after acrolein instillation did not alter referred hyperalgesia. Lidocaine treatment prior to or after induction of cystitis reduced NGF content in the bladder. Conclusions These results indicate that pre-treatment with lidocaine attenuates referred hyperalgesia associated with cystitis. Lidocaine treatment 4 hr after induction of cystitis failed to prevent referred hyperalgesia despite a similar decrease in bladder NGF. Neurourol. Urodynam. © 2009 Wiley-Liss, Inc.

Visceral inflammation, including that arising from bladder inflammation, reduces the threshold to sensation of innocuous or noxious stimuli applied to peripheral structures (referred hyperalgesia). Cystitis may induce transient or persistent plastic changes mediated by neurotrophins, particularly nerve growth factor (NGF), which contribute to increased nociceptive input. In this study, acute or subacute cystitis was induced in female rats by one or three (at 72-h intervals) 400-μl intravesical instillations of 1 mM acrolein. Sensitivity of the hindpaws to mechanical and thermal stimuli was determined before and 4, 24, 48, 72, and 96 h after treatment. Other groups of rats were treated with intravesical or intrathecal k252a [a nonspecific antagonist of tyrosine kinase (trk) receptors, including trkA, the high-affinity receptor for NGF] before the first or third acrolein instillation. Some rats were intraperitoneally injected with specific NGF-neutralizing antiserum or normal serum before acrolein instillation. Acute and subacute cystitis induced mechanical, but not thermal, referred hyperalgesia that was attenuated by intravesical pretreatment with k252a. Systemic treatment with NGF-neutralizing antiserum before instillation of acrolein suppressed subsequent mechanical referred hyperalgesia. Expression of NGF was increased within the bladder by acute or subacute cystitis and in L6/S1 dorsal root ganglia by subacute cystitis. These results suggest that the bladder-derived NGF acting via trk receptors at least partially mediates peripheral sensitization to mechanical stimuli associated with acute and subacute acrolein-induced cystitis.

OBJECTIVE To develop a method of direct intravesical administration of acrolein and evaluate the severity of cystitis in response to increasing doses of acrolein in female C57BL/6N (C57) mice, with further studies to compare the severity of acute acrolein-induced cystitis among C57, C3H/HeJ (HeJ), and C3H/OuJ (OuJ) strains of mice, as chemical cystitis produced by the systemic administration of cyclophosphamide is thought to result from renal excretion of hepatic metabolites, particularly acrolein. MATERIALS AND METHODS Doses of acrolein (0–1000 µg, 15 µL total volume) were instilled into the bladders of C57 female mice; the bladders were removed 4 or 24 h later, weighed, and processed for histology. Acrolein (6 or 10 µg; 15 µL) was instilled into the bladders of C57, HeJ and OuJ female mice, the bladders removed 4 or 24 h later, weighed, and processed for standard histology and immunohistochemical detection of uroplakin. RESULTS Increasing doses of acrolein up to 100–200 µg caused a linear increase in bladder weight and greater histological evidence of inflammation. Doses of >200 µg caused submaximal increases in bladder weight, apparently due to structural damage of the bladder. Bladder weight and submucosal oedema were consistently greater in C57 and HeJ than OuJ mice. Treatment with acrolein caused loss of urothelium along with uroplakin in some areas of all bladder sections 4 h after treatment. Bladders from C57 mice had some loss of urothelium 24 h after instillation of 6 or 10 µg acrolein, but urothelium and uroplakin covered nearly all the surface of bladders of HeJ and OuJ mice 24 h after treatment. There were significantly more white blood cells in bladders from C57 or HeJ mice than in bladders from OuJ mice 24 h after an instillation of 6 or 10 µg acrolein. CONCLUSIONS Intravesical instillation of acrolein produces dose-dependent cystitis in mice. OuJ mice appear relatively more resistant to irritant effects of intravesical acrolein than C57 or HeJ mice, and future studies will be directed at identifying genetic causes for these differences.