Mika Joanna, Osikowicz Maria, Makuch Wioletta, Przewlocka Barbara
Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Cracow, Poland.
Eur J Pharmacol. 2007 Apr 10;560(2-3):142-9. doi: 10.1016/j.ejphar.2007.01.013. Epub 2007 Jan 19.
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 (30 microg; 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.
最近的研究表明，在神经病变中被强烈激活的小胶质细胞可影响异常性疼痛和痛觉过敏的发展。在此我们证明，在大鼠慢性缩窄性损伤（CCI）前16小时和1小时以及神经结扎后每天两次连续7天腹腔注射（i.p.）米诺环素（15、30、50mg/kg），一种有效的小胶质细胞激活抑制剂，可显著减轻在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）。此外，观察到运动功能有40%的改善。在小鼠中，按照相同方案腹腔注射米诺环素（30mg/kg）或己酮可可碱（20mg/kg）也显著降低了CCI后第7天的异常性疼痛和痛觉过敏。在预先和反复注射米诺环素的组中（大鼠的von Frey试验中分别为18g对22g；冷板试验中分别为13秒对20秒，小鼠中分别为1.2g对2.2g；7.5秒对10秒）或己酮可可碱（小鼠中分别为1.3g对3g；7.6秒对15秒），吗啡（10mg/kg；腹腔注射）的抗异常性疼痛和抗痛觉过敏作用显著增强。通过腰椎穿刺给予小鼠的吗啡（30μg；鞘内注射）的抗异常性疼痛和抗痛觉过敏作用在米诺环素治疗组中也显著增强（分别为1.2g对2.2g；7.5秒对11秒）。这些发现表明，预先和反复给予胶质细胞抑制剂可抑制异常性疼痛和痛觉过敏的发展，并增强吗啡在大鼠和小鼠神经性疼痛模型中的作用。
