Woon Eric, Zhang Shaopeng, Chen Longtu, Kuchel George, Bartley Jenna, Feng Bin
Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut; UConn Center on Aging, School of Medicine, UConn Health, Farmington, Connecticut; Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut.
Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut.
J Pharmacol Exp Ther. 2025 Jun;392(6):103587. doi: 10.1016/j.jpet.2025.103587. Epub 2025 Apr 22.
Bladder-related disorders, such as underactive or overactive bladder and chronic pelvic pain syndromes, are typically studied by recording cystometrogram and visceromotor responses (VMRs) to urinary bladder distension (UBD) in anesthetized rats. Recently, similar studies have been conducted in mice due to their suitability for genetic manipulation. However, assessing bladder physiology and pain in aged mice remains challenging due to inconsistencies in anesthesia. Here, we optimized a urethane anesthesia protocol to enable robust cystometrogram (CMG) recordings and VMR in female mice of 2 different age groups: mature (10-12 months) and aged (18-22 months). Mice were first anesthetized with 1.75% isoflurane inhalation for the surgical implantation of a bladder catheter and stainless-steel wire electrodes to the external oblique musculature for delivering bladder distension and recording muscular response respectively. Another catheter was placed intraperitoneally for continuous delivery of urethane (0.15-0.23 g/kg per hour for 2 hours). CMG was measured by delivering slow bladder filling (1.5 mL/h) through the catheter while recording intravesical pressure, VMR responses from external oblique musculature, and micturition volume. Afterwards, VMR response to UBD was recorded. In another cohort, both CMG and VMR response to UBD were assessed before and after intravesical infusion of 0.5% acetic acid and 0.1% lidocaine. Intravesical infusion of acetic acid significantly enhanced the VMR to grader bladder distension and disrupted the regular micturition cycles, which were normalized by intravesical lidocaine. This anesthesia protocol produced robust CMG and VMR recordings for 2 hours in mice of both age groups, enabling focused studies to advance mechanistic understanding of bladder-related disorders. SIGNIFICANCE STATEMENT: A urethane anesthesia protocol was optimized for robust cystometrogram and visceromotor response recordings in mature and aged mice. This model allows assessment of bladder physiology and pain, demonstrating that acetic acid disrupts micturition and enhances pain responses, which lidocaine normalizes.
膀胱相关疾病，如膀胱活动低下或亢进以及慢性盆腔疼痛综合征，通常通过在麻醉大鼠中记录膀胱内压测量图和对膀胱扩张（UBD）的内脏运动反应（VMRs）来进行研究。最近，由于小鼠适合进行基因操作，类似的研究也在小鼠中开展。然而，由于麻醉的不一致性，评估老年小鼠的膀胱生理学和疼痛仍然具有挑战性。在此，我们优化了一种氨基甲酸乙酯麻醉方案，以在2个不同年龄组的雌性小鼠中实现可靠的膀胱内压测量图（CMG）记录和VMR：成熟小鼠（10 - 12个月）和老年小鼠（18 - 22个月）。首先用1.75%异氟烷吸入麻醉小鼠，以便进行膀胱导管和不锈钢丝电极的手术植入，分别用于向腹外斜肌输送膀胱扩张刺激和记录肌肉反应。另一个导管经腹腔放置用于持续输注氨基甲酸乙酯（0.15 - 0.23 g/kg每小时，持续2小时）。通过导管以缓慢的膀胱充盈速度（1.5 mL/h）进行膀胱充盈，同时记录膀胱内压、腹外斜肌的VMR反应和排尿量，以此来测量CMG。之后，记录对UBD的VMR反应。在另一组实验中，在膀胱内注入0.5%乙酸和0.1%利多卡因之前和之后，评估CMG和对UBD的VMR反应。膀胱内注入乙酸显著增强了对分级膀胱扩张的VMR，并扰乱了正常的排尿周期，而膀胱内注入利多卡因可使其恢复正常。这种麻醉方案在两个年龄组的小鼠中均能产生持续2小时的可靠CMG和VMR记录，有助于开展针对性研究，以增进对膀胱相关疾病机制的理解。意义声明：优化了一种氨基甲酸乙酯麻醉方案，用于在成熟和老年小鼠中进行可靠的膀胱内压测量图和内脏运动反应记录。该模型可用于评估膀胱生理学和疼痛，表明乙酸会扰乱排尿并增强疼痛反应，而利多卡因可使其恢复正常。
