Optimization of a Pain Model: Effects of Body Temperature and Anesthesia on Bladder Nociception in Mice
Optimization of a Pain Model: Effects of Body Temperature and Anesthesia on Bladder Nociception in Mice
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DOI：
10.1371/journal.pone.0079617
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发表时间：
2013-11-05
期刊：
影响因子：
3.7
通讯作者：
Kolber, Benedict J.
中科院分区：
文献类型：
--
作者：
Sadler, Katelyn E.;Stratton, Jarred M.;Kolber, Benedict J.
间质性膀胱炎/膀胱疼痛综合征（IC/BPS）是一种使人衰弱的泌尿系统疾病，对治疗有抵抗力，而且了解甚少。为了确定新的分子治疗靶点并阐明神经系统对IC/BPS的贡献，已经开发了许多啮齿动物膀胱疼痛模型。在这项研究中，我们评估了麻醉诱导和温度变化的影响，在小鼠模型的膀胱疼痛称为膀胱扩张（UBD）。在该模型中，使用压缩空气将膀胱扩张到不同的压力，同时电极记录来自覆盖的腹肌的反射性内脏反应（VMR）。在UBD之前通常使用两种异氟烷诱导模型：持续约30分钟的短方法和持续约90分钟的长方法。用其中一种方法麻醉动物，然后使其经历三组分级膀胱扩张。尽管测试参数相同，但在短麻醉方案后进行的扩张彼此显著不同;当使用长麻醉方案时，未观察到相同的效果。为了确定温度对VMR的影响，将动物置于37.5（正常小鼠体温）、35.5和33.5 ℃的三个分级扩张组中。在33.5和35.5 ℃下进行的扩张显著低于在37.5 ℃下进行的扩张。此外，蛋白质印迹分析显示，与37.5摄氏度相比，体温保持在33.5摄氏度的动物在膀胱扩张后脊髓磷酸化细胞外信号调节激酶2（pERK 2）水平的增加显著较小。这些结果强调了麻醉对疼痛样变化的动态影响的重要性，以及在进行UBD时密切监测温度的重要性。为了成功解释VMR并转化为人类疾病，体温应保持在37.5 ℃，异氟烷诱导应在90分钟内逐渐减少。
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating urological condition that is resistant to treatment and poorly understood. To determine novel molecular treatment targets and to elucidate the contribution of the nervous system to IC/BPS, many rodent bladder pain models have been developed. In this study we evaluated the effects of anesthesia induction and temperature variation in a mouse model of bladder pain known as urinary bladder distension (UBD). In this model compressed air is used to distend the bladder to distinct pressures while electrodes record the reflexive visceromotor response (VMR) from the overlying abdominal muscle. Two isoflurane induction models are commonly used before UBD: a short method lasting approximately 30 minutes and a long method lasting approximately 90 minutes. Animals were anesthetized with one of the methods then put through three sets of graded bladder distensions. Distensions performed following the short anesthesia protocol were significantly different from one another despite identical testing parameters; this same effect was not observed when the long anesthesia protocol was used. In order to determine the effect of temperature on VMRs, animals were put through three graded distension sets at 37.5 (normal mouse body temperature), 35.5, and 33.5 degrees C. Distensions performed at 33.5 and 35.5 degrees C were significantly lower than those performed at 37.5 degrees C. Additionally, Western blot analysis revealed significantly smaller increases in spinal levels of phosphorylated extracellular-signal regulated kinase 2 (pERK2) following bladder distension in animals whose body temperature was maintained at 33.5 degrees C as opposed to 37.5 degrees C. These results highlight the significance of the dynamic effects of anesthesia on pain-like changes and the importance of close monitoring of temperature while performing UBD. For successful interpretation of VMRs and translation to human disease, body temperature should be maintained at 37.5 degrees C and isoflurane induction should gradually decrease over the course of 90 minutes.