Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Eur J Pharmacol. 2018 Sep 5;834:221-229. doi: 10.1016/j.ejphar.2018.07.011. Epub 2018 Jul 27.
It seems that histamine release in the site of neuronal injury could contribute to the neuropathic pain mechanism. In the present study, we investigated the anti-allodynic effects of chronic administration of different classes of histamine H and H receptor antagonists on neuropathic nociceptive behavior following tibial nerve transection (TNT) in rats. Peripheral neuropathy was induced by TNT surgery. We performed acetone tests (AT) to record cold allodynia, Von Frey tests (VFT) to measure mechanical allodynia, double plate test (DPT) to evaluate thermal place preference/avoidance and open field test (OFT) for evaluation of animal activity. TNT rats showed a significant mechanical and cold allodynia compared to the sham group. Chlorpheniramine (5 and 15 mg/kg, i.p) significantly attenuated cold allodynia and prevented cold plate avoidance behavior and at the dose of 15 mg/kg remarkably decreased mechanical allodynia. Fexofenadine (10 and 30 mg/kg, p.o) significantly attenuated the mechanical allodynia and prevented cold plate avoidance. Ranitidine (5 and 15 mg/kg, i.p) significantly prevented cold plate avoidance behavior and at the dose of 15 mg/kg notably improved mechanical and cold allodynia. Famotidine (1 and 3 mg/kg, p.o) was ineffective on all nociceptive tests. Gabapantin (100 mg/kg, p.o) significantly improved all types of nociceptive behaviors. These results indicate that both blood brain barrier penetrating (chlorpheniramine) and poorly penetrating (fexofenadine) histamine H receptor antagonists could improve the neuropathic pain sign, but only the blood brain barrier penetrating histamine H receptor antagonist (ranitidine) could produce anti-allodynic effects in the TNT model of neuropathic pain in rats.
似乎神经元损伤部位的组胺释放可能有助于神经病理性疼痛机制。在本研究中，我们研究了不同类别的组胺 H1 和 H2 受体拮抗剂在大鼠坐骨神经横断（TNT）后慢性给药对神经病理性伤害感受行为的抗伤害作用。周围神经病变通过 TNT 手术诱导。我们进行了丙酮试验（AT）以记录冷感觉异常，von Frey 试验（VFT）测量机械感觉异常，双板试验（DPT）评估热位置偏好/回避，以及开放式试验（OFT）用于评估动物活动。与假手术组相比，TNT 大鼠表现出明显的机械性和冷感觉异常。氯苯那敏（5 和 15mg/kg，ip）显著减轻冷感觉异常，并防止冷板回避行为，且在 15mg/kg 剂量下显著降低机械性感觉异常。非索非那定（10 和 30mg/kg，po）显著减轻机械性感觉异常，并防止冷板回避。雷尼替丁（5 和 15mg/kg，ip）显著防止冷板回避行为，且在 15mg/kg 剂量下显著改善机械性和冷感觉异常。法莫替丁（1 和 3mg/kg，po）对所有伤害性测试均无效。加巴喷丁（100mg/kg，po）显著改善所有类型的伤害性行为。这些结果表明，血脑屏障穿透性（氯苯那敏）和非穿透性（非索非那定）组胺 H1 受体拮抗剂均可改善神经病理性疼痛体征，但只有血脑屏障穿透性组胺 H1 受体拮抗剂（雷尼替丁）可在大鼠神经病理性疼痛的 TNT 模型中产生抗伤害作用。
