Cyclophosphamide-induced cystitis in freely-moving conscious rats: Behavioral approach to a new model of visceral pain
Cyclophosphamide-induced cystitis in freely-moving conscious rats: Behavioral approach to a new model of visceral pain
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DOI：
10.1016/s0022-5347(05)67495-2
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发表时间：
2000-07-01
影响因子：
6.6
通讯作者：
Eschalier, A
中科院分区：
文献类型：
--
作者：
Boucher, M;Meen, M;Eschalier, A
目的：使用行为方法建立大鼠内脏疼痛模型。环磷酰胺 (CP) 是一种抗肿瘤药物，已知通过其主要有毒代谢物丙烯醛对膀胱壁产生毒性作用，用于诱发膀胱炎。材料和方法：环磷酰胺的给药剂量为 50、100 和 200 mg/kg。 ip给雄性大鼠，观察它们的行为并评分。单独使用吗啡（0.5 至 4 毫克/公斤静脉注射）对 CP 诱导的行为改变的影响进行了测试，分别单独使用和在纳洛酮（1 毫克/公斤皮下注射）之后使用。另外，注射CP后90分钟，即给予吗啡时，切除一些大鼠的膀胱进行组织学检查。最后，为了表明膀胱对于 CP 诱导的行为改变至关重要，雌性大鼠还接受了 200 mg/kg 剂量的 CP。 ip和20毫克。通过膀胱内途径，丙烯醛剂量为 0.5 mg。通过膀胱内途径，5 mg./kg。 i.v. 结果：CP 剂量相关地诱导雄性大鼠显着的行为改变：呼吸频率降低、闭眼和出现特定姿势。吗啡剂量依赖性地逆转这些行为障碍。剂量为0.5毫克/公斤。 CP 200 mg./kg 引起的行为评分降低了近 50%。用纳洛酮预处理可以完全防止这种效应。在给予吗啡时，观察到膀胱壁的组织学改变，例如绒毛膜和肌肉层水肿。在雌性大鼠中，CP 200 mg./kg。 ip产生了与雄性大鼠中观察到的相同的显着行为改变。给药剂量为20mg。膀胱灌注时，CP 不会产生任何行为影响，而丙烯醛则为 0.5 mg。膀胱内诱导的行为改变与 CP 200 mg./kg 下的行为改变相同。 i.p.，具有相同的最大水平。相反，丙烯醛5mg/kg。静脉注射结论：总体而言，这些结果表明，CP 诱发的膀胱炎实验模型可能是一种有趣的新的炎症性内脏疼痛行为模型，可以更好地了解这些疼痛综合征，从而提供更好的治疗方法。
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.