Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; TRP Research Platform Leuven (TRPLe), Leuven, Belgium.
Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; TRP Research Platform Leuven (TRPLe), Leuven, Belgium.
Eur Urol. 2015 Oct;68(4):655-61. doi: 10.1016/j.eururo.2015.03.037. Epub 2015 Apr 3.
Acute exposure of part of the skin to cold stimuli can evoke urinary urgency, a phenomenon termed acute cold-induced urgency (ACIU). Despite its high prevalence, particularly in patients with overactive bladder, little is known about the mechanisms that induce ACIU.
To develop an animal model of ACIU and test the involvement of cold-activated ion channels transient receptor potential (TRP) M8 and TRPA1.
DESIGN, SETTING, AND PARTICIPANTS: Intravesical pressure and micturition were monitored in female mice (wild-type C57BL/6J, Trpa1(-/-), Trpm8(+/+), and Trpm8(-/-)) and Sprague Dawley rats.
An intravesical catheter was implanted. Localized cooling of the skin was achieved using a stream of air or topical acetone. The TRPM8 antagonist (N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide (AMTB) or vehicle was injected intraperitoneally.
Frequencies of bladder contractions and voids in response to sensory stimuli were compared using the Mann-Whitney or Kruskal-Wallis test.
Brief, innocuously cold stimuli applied to different parts of the skin evoked rapid bladder contractions and voids in anesthetized mice and rats. These responses were strongly attenuated in Trpm8(-/-) mice and in rats treated with AMTB. As rodent bladder physiology differs from that of humans, it is difficult to directly extrapolate our findings to human patients.
Our findings indicate that ACIU is an evolutionarily conserved reflex rather than subconscious conditioning, and provide a useful in vivo model for further investigation of the underlying mechanisms. Pharmacological inhibition of TRPM8 may be useful for treating ACIU symptoms in patients.
Brief cold stimuli applied to the skin can evoke a sudden desire to urinate, which can be highly bothersome in patients with overactive bladder. We developed an animal model to study this phenomenon, and found that it depends on a specific molecular cold sensor, transient receptor potential M8 (TRPM8). Pharmacological inhibition of TRPM8 may alleviate acute cold-induced urinary urgency in humans.
皮肤的一部分暴露于冷刺激会引起尿急，这种现象称为急性冷诱导性尿急（ACIU）。尽管它的发病率很高，尤其是在膀胱过度活动症患者中，但对于引起 ACIU 的机制知之甚少。
建立 ACIU 的动物模型，并测试冷激活离子通道瞬时受体电位（TRP）M8 和 TRPA1 的参与情况。
设计、地点和参与者：在雌性小鼠（野生型 C57BL/6J、Trpa1(-/-)、Trpm8(+/+)和 Trpm8(-/-)）和 Sprague Dawley 大鼠中监测膀胱内压和排尿。
植入膀胱内导管。使用气流或局部丙酮实现皮肤局部冷却。腹腔内注射 TRPM8 拮抗剂（N-(3-氨基丙基)-2-[[(3-甲基苯基)甲基]氧基]-N-(2-噻吩基甲基)苯甲酰胺（AMTB）或载体。
使用 Mann-Whitney 或 Kruskal-Wallis 检验比较对感觉刺激的膀胱收缩和排空频率。
短暂的、无害的冷刺激应用于皮肤的不同部位会引起麻醉小鼠和大鼠的快速膀胱收缩和排空。这些反应在 Trpm8(-/-)小鼠和用 AMTB 治疗的大鼠中被强烈减弱。由于啮齿动物的膀胱生理学与人类不同，因此很难直接将我们的发现推断为人类患者。
我们的发现表明，ACIU 是一种进化上保守的反射，而不是潜意识的条件反射，并提供了一种有用的体内模型，用于进一步研究潜在的机制。TRPM8 的药理学抑制可能对治疗膀胱过度活动症患者的 ACIU 症状有用。
皮肤受到短暂的冷刺激会引起突然的排尿欲望，这在膀胱过度活动症患者中会非常困扰。我们开发了一种动物模型来研究这种现象，发现它依赖于一种特定的分子冷传感器，即瞬时受体电位 M8（TRPM8）。TRPM8 的药理学抑制可能会缓解人类急性冷诱导性尿急。
