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CYCLOPHOSPHAMIDE-INDUCED CYSTITIS IN FREELY-MOVING CONSCIOUS RATS: BEHAVIORAL APPROACH TO A NEW MODEL OF VISCERAL PAIN

医学 环磷酰胺 膀胱疼痛综合征 内脏痛 麻醉 间质性膀胱炎 内科学 化疗 伤害 泌尿系统 受体
作者
Michel Boucher,Murielle Méen,JEAN-PAUL CODRON,FRANCOIS COUDORE,Jean‐Louis Kémény,Alain Eschalier
出处
期刊:The Journal of Urology [Lippincott Williams & Wilkins]
卷期号:164 (1): 203-208 被引量:102
标识
DOI:10.1016/s0022-5347(05)67495-2
摘要

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Jul 2000CYCLOPHOSPHAMIDE-INDUCED CYSTITIS IN FREELY-MOVING CONSCIOUS RATS: BEHAVIORAL APPROACH TO A NEW MODEL OF VISCERAL PAIN MICHEL BOUCHER, MURIELLE MEEN, JEAN-PAUL CODRON, FRANCOIS COUDORE, JEAN-LOUIS KEMENY, and ALAIN ESCHALIER MICHEL BOUCHERMICHEL BOUCHER More articles by this author , MURIELLE MEENMURIELLE MEEN More articles by this author , JEAN-PAUL CODRONJEAN-PAUL CODRON More articles by this author , FRANCOIS COUDOREFRANCOIS COUDORE More articles by this author , JEAN-LOUIS KEMENYJEAN-LOUIS KEMENY More articles by this author , and ALAIN ESCHALIERALAIN ESCHALIER More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)67495-2AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: To develop a model of visceral pain in rats using a behavioral approach. Cyclophosphamide (CP), an antitumoral agent known to produce toxic effects on the bladder wall through its main toxic metabolite acrolein, was used to induce cystitis. Materials and Methods: CP was administered at doses of 50, 100 and 200 mg./kg. i.p. to male rats, and their behavior observed and scored. The effects of morphine (0.5 to 4 mg./kg. i.v.) on CP-induced behavioral modifications were tested administered alone and after naloxone (1 mg./kg. s.c.). In addition, 90 minutes after CP injection, that is, at the time of administration of morphine, the bladder was removed in some rats for histological examination. Finally, to show that the bladder is essential for the CP-induced behavioral modifications, female rats also received CP at doses of 200 mg./kg. i.p. and of 20 mg. by the intravesical route, and acrolein at doses of 0.5 mg. by the intravesical route and of 5 mg./kg. i.v. Results: CP dose-relatedly induced marked behavioral modifications in male rats: breathing rate decrease, closing of the eyes and occurrence of specific postures. Morphine dose-dependently reversed these behavioral disorders. A dose of 0.5 mg./kg. produced a reduction of almost 50% of the behavioral score induced by CP 200 mg./kg. This effect was completely prevented by pretreatment with naloxone. At the time of administration of morphine, histological modifications of the bladder wall, such as chorionic and muscle layer edema, were observed. In female rats, CP 200 mg./kg. i.p. produced the same marked behavioral modifications as those observed in male rats. Administered at the dose of 20 mg. intravesically, CP did not produce any behavioral effects, whereas acrolein at 0.5 mg. intravesically induced behavioral modifications identical to those under CP 200 mg./kg. i.p., with the same maximal levels. Conversely, acrolein 5 mg./kg. i.v. did not produce any behavioral effects at all. Conclusions: Overall, these results indicate that this experimental model of CP-induced cystitis may be an interesting new behavioral model of inflammatory visceral pain, allowing a better understanding of these painful syndromes and thus a better therapeutic approach to them. References 1 : A model for the study of visceral pain states: chronic inflammation of the chronic decerebrate rat urinary bladder by irritant chemicals. Pain1987; 28: 109. Google Scholar 2 : A method for studying pain arising from the urinary bladder in conscious, freely-moving rats. J Urol1989; 141: 148. Link, Google Scholar 3 : Influence of the nervous system on experimentally induced urethral inflammation. Neurosci Lett1990; 115: 183. Google Scholar 4 : Increased c-fos expression in spinal neurons after irritation of the lower urinary tract in the rat. J Neurosci1992; 12: 4878. Google Scholar 5 : Behavioral responses to uterine or vaginal distension in the rat. Pain1995; 61: 121. 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Google Scholar From Inserm EPI9904 (Laboratoire de Physiologie, Laboratoire de Pharmacologie, and Laboratoire de Toxicologie, Faculté de Pharmacie), the Laboratoire d’Anatomie-Pathologique, CHU Gabriel Montpied, and the Laboratoire de Pharmacologie Médicale, Faculté de Médecine, University of Auvergne, Clermont-Ferrand, France© 2000 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byPessina F, Capasso R, Borrelli F, Aveta T, Buono L, Valacchi G, Fiorenzani P, Di Marzo V, Orlando P and Izzo A (2018) Protective Effect of Palmitoylethanolamide in a Rat Model of CystitisJournal of Urology, VOL. 193, NO. 4, (1401-1408), Online publication date: 1-Apr-2015.Takahara Y, Suzuki A, Maeda M, Kawashima H, Nakatani T and Kiyama H (2018) Expression of Pancreatitis Associated Proteins in Urothelium and Urinary Afferent Neurons Following Cyclophosphamide Induced CystitisJournal of Urology, VOL. 179, NO. 4, (1603-1609), Online publication date: 1-Apr-2008.BON K, LICHTENSTEIGER C, WILSON S and MOGIL J (2018) Characterization of Cyclophosphamide Cystitis, a Model of Visceral and Referred Pain, in the Mouse: Species and Strain DifferencesJournal of Urology, VOL. 170, NO. 3, (1008-1012), Online publication date: 1-Sep-2003.MEEN M, COUDORE-CIVIALE M, ESCHALIER A and BOUCHER M (2018) INVOLVEMENT OF HYPOGASTRIC AND PELVIC NERVES FOR CONVEYING CYSTITIS INDUCED NOCICEPTION IN CONSCIOUS RATSJournal of Urology, VOL. 166, NO. 1, (318-322), Online publication date: 1-Jul-2001. Volume 164Issue 1July 2000Page: 203-208 Advertisement Copyright & Permissions© 2000 by American Urological Association, Inc.Keywordsurinary bladderbehavioral approachvisceral paincystitiscyclophosphamideratMetricsAuthor Information MICHEL BOUCHER More articles by this author MURIELLE MEEN More articles by this author JEAN-PAUL CODRON More articles by this author FRANCOIS COUDORE More articles by this author JEAN-LOUIS KEMENY More articles by this author ALAIN ESCHALIER More articles by this author Expand All Advertisement PDF downloadLoading ...
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