Effects of Phenazopyridine on Rat Bladder Primary Afferent Activity, and Comparison With Lidocaine and Acetaminophen
Effects of Phenazopyridine on Rat Bladder Primary Afferent Activity, and Comparison With Lidocaine and Acetaminophen
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DOI：
10.1002/nau.20886
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发表时间：
2010-01-01
影响因子：
2
通讯作者：
Wyndaele, Jean-Jacques
中科院分区：
文献类型：
--
作者：
Aizawa, Naoki;Wyndaele, Jean-Jacques
目的：非那吡啶的临床适应症尚不清楚，临床上已用于膀胱炎和膀胱疼痛综合征/间质性膀胱炎等膀胱感觉增强的疾病。我们探讨了非那吡啶对传入神经活动的影响，直接测量A δ和C纤维在大鼠，并比较结果与利多卡因（局部麻醉剂）和对乙酰氨基酚（镇痛剂）的影响。方法：采用雌性Sprague道利大鼠。在乌拉坦麻醉下，通过电刺激左侧骨盆神经和膀胱扩张，在L 6背根中识别出主要源自膀胱的单个神经纤维。通过传导速度（2.5m/sec），纤维被定义为Δ-纤维或C-纤维。在给药前测量响应于恒定膀胱充盈的传入活动。然后，静脉内施用非那吡啶（0.1- 3 mg/kg）或利多卡因（0.3-3 mg/kg）或对乙酰氨基酚（1-10 mg/kg）。给药后，再次测量膀胱填充物的传入活动。结果：所有药物均能显著增加膀胱顺应性，并呈剂量依赖性。分离出28条单传入纤维（AS纤维：n = 13，C纤维：n = 15）。静脉注射非那吡啶剂量依赖性地显著降低AS纤维活性，但不降低C纤维活性。对乙酰氨基酚仅显著降低AS-纤维活性，但不完全呈剂量依赖性。利多卡因抑制A δ和C纤维活动。结论：非那吡啶可直接抑制正常大鼠膀胱的A δ纤维。这一发现可能解释了其在膀胱超敏反应条件下的临床效果。Neurorol。尿动力药29：1445-1450，2010. (C)2010 Wiley-Liss，Inc.
Aims: The clinical indication of phenazopyridine is unclear, it has been used clinically in conditions with increased bladder sensation as in cystitis and bladder pain syndrome/interstitial cystitis. We explored the effect of phenazopyridine on afferent nerve activity by direct measurement of both A delta- and C-fibers in the rat, and compared the outcome with the effects of lidocaine (a local anesthetic) and of acetaminophen (an analgesic). Methods: Female Sprague Dawley rats were used. Under urethane anesthesia, single nerve fibers primarily originating from the bladder were identified in the L6 dorsal root by electrical stimulation of the left pelvic nerve and by bladder distention. By conduction velocity (2.5 m/sec) the fibers were defined as A delta-fiber or C-fiber. The afferent activity in response to constant bladder filling was measured before the drug administration. Then, phenazopyridine (0.1- 3 mg/kg) or lidocaine (0.3-3 mg/kg) or acetaminophen (1-10 mg/kg) was administrated intravenously. After drug administration, the afferent activity of bladder fillings was measured again. Results: All drugs significantly increased bladder compliance, in a dose-dependent way. Twenty-eight single afferent fibers (AS-fibers: n = 13, C-fibers: n = 15) were isolated. Intravenous administration of phenazopyridine significantly decreased dose-dependently only the AS-fiber but not the C-fiber activity. Also acetaminophen significantly decreased only AS-fiber activity, but it was not dose-dependently completely. Lidocaine inhibited both the A delta- and C-fiber activities. Conclusions: This study shows that phenazopyridine can directly inhibit the mechanosensitive A delta-fibers in the normal rat bladder. This finding might explain its clinical effect in conditions of bladder hypersensitivity. Neurourol. Urodynanz. 29:1445-1450, 2010. (C) 2010 Wiley-Liss, Inc.