Minocycline and pentoxifylline attenuate allodynia and hyperalgesia and potentiate the effects of morphine in rat and mouse models of neuropathic pain
Minocycline and pentoxifylline attenuate allodynia and hyperalgesia and potentiate the effects of morphine in rat and mouse models of neuropathic pain
复制标题
DOI：
10.1016/j.ejphar.2007.01.013
复制
发表时间：
2007-04-10
影响因子：
5
通讯作者：
Przewlocka, Barbara
中科院分区：
文献类型：
--
作者：
Mika, Joanna;Osikowicz, Maria;Przewlocka, Barbara
最近的研究表明，在神经病变中强烈激活的小胶质细胞可以影响异常性疼痛和痛觉过敏的发展。在这里，我们证明，先发制人和重复腹腔注射（损伤前 16 小时和 1 小时，然后在神经结扎后每天两次，持续 7 天）米诺环素（15；30；50 mg/kg）（一种小胶质细胞活化的有效抑制剂），显着减轻慢性缩窄性损伤（CCI）后第 3、5、7 天测量的异常性疼痛（von Frey 试验）和痛觉过敏（冷板试验）。在老鼠身上。此外，观察到运动功能提高了 40%。在小鼠中，按照相同的方案腹腔注射米诺环素 (30 mg/kg) 或己酮可可碱 (20 mg/kg) 也可显着减少 CCI 后第 7 天的异常性疼痛和痛觉过敏。在先发制人和重复注射米诺环素的组中，吗啡（10 mg/kg；腹腔注射）的抗痛觉和痛觉过敏作用显着增强（von Frey 试验，18 g 与 22 g；冷板试验，大鼠中 13 s 与 20 s；小鼠中 1.2 g 与 2.2 g；7.5 s 与 10 s；分别）或己酮可可碱（小鼠中分别为 1.3 g 与 3 g；7.6 秒与 15 秒）。通过腰椎穿刺给予小鼠的吗啡（3·0μg；i.t.）的抗痛觉和抗痛觉过敏作用在米诺环素治疗组中也显着增强（分别为1.2g对2.2g；7.5秒对11秒）。这些发现表明，预先和重复施用神经胶质抑制剂可抑制异常性疼痛和痛觉过敏的发生，并增强吗啡在大鼠和小鼠神经性疼痛模型中的作用。 (c) 2007 Elsevier B.V. 保留所有权利。
Recent research has shown that microglial cells which are strongly activated in neuropathy can influence development of allodynia and hyperalgesia. Here we demonstrated that preemptive and repeated i.p., administration (16 h and 1 h before injury and then after nerve ligation twice daily for 7 days) of minocycline (15; 30; 50 mg/kg), a potent inhibitor of microglial activation, significantly attenuated the allodynia (von Frey test) and hyperalgesia (cold plate test) measured on day 3, 5, 7 after chronic constriction injury (CCI) in rats. Moreover, the 40% improvement of motor function was observed. In mice, i.p., administration of minocycline (30 mg/kg) or pentoxifylline (20 mg/kg) according to the same schedule also significantly decreased allodynia and hyperalgesia on day 7 after CCI. Antiallodynic and antihyperalgesic effect of morphine (10 mg/kg; i.p.) was significantly potentiated in groups preemptively and repeatedly injected with minocycline (von Frey test, 18 g versus 22 g; cold plate test, 13 s versus 20 s in rats and 1.2 g versus 2.2 g; 7.5 s versus 10 s in mice; respectively) or pentoxifylline (1.3 g versus 3 g; 7.6 s versus 15 s in mice; respectively). Antiallodynic and antihyperalgesic effect of morphine (3 0 mu g; i.t.) given by lumbar puncture in mice was also significantly potentiated in minocycline-treated group (1.2 g versus 2.2 g; 7.5 s versus 11 s; respectively). These findings indicate that preemptive and repeated administration of glial inhibitors suppresses development of allodynia and hyperalgesia and potentiates effects of morphine in rat and mouse models of neuropathic pain. (c) 2007 Elsevier B.V. All rights reserved.