Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: Bilateral effect after unilateral injection
Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: Bilateral effect after unilateral injection
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DOI：
10.1016/j.ejphar.2010.01.020
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发表时间：
2010-05-10
影响因子：
5
通讯作者：
Lackovic, Zdravko
中科院分区：
文献类型：
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作者：
Bach-Rojecky, Lidija;Salkovic-Petrisic, Melita;Lackovic, Zdravko
我们研究了A型肉毒杆菌毒素（BTX-A）在大鼠糖尿病神经病理性疼痛模型中的抗伤害性感受活性。通过单次腹腔注射链脲佐菌素（80 mg/kg）使雄性Wistar大鼠患糖尿病。机械和热刺激的敏感性测定爪压力和热板试验，分别。福尔马林试验用于测量对化学刺激的敏感性。与非糖尿病组相比，疼痛阈值降低至少25%的糖尿病动物被认为是神经病性的，并皮下（3、5和7 U/kg）或鞘内（1 U/kg）注射BTX-A。在几个时间点测量机械和热灵敏度。在外周应用后，BTX-A（5和7 U/kg）不仅降低了同侧的机械和热过敏，而且也降低了对侧的机械和热过敏。BTX-A注射后5天开始产生抗伤害效应，并持续至少15天。糖尿病动物中福尔马林诱导的超敏反应也被消除。当鞘内应用时，BTX-A（1U/kg）在24小时内减少糖尿病性痛觉过敏，支持BTX-A从外周注射部位到中枢神经系统的逆行轴突运输的假设。这里呈现的结果证明了在患有糖尿病神经病变的动物中单次注射BTX-A后持久的疼痛减轻。单侧毒素应用后双侧疼痛减轻和鞘内注射后起效更快的低剂量有效性表明中枢神经系统参与BTX-A在疼痛性糖尿病神经病变中的抗伤害性作用。(C)2010 Elsevier B. V.保留所有权利。
We investigated antinociceptive activity of botulinum toxin type A (BTX-A) in a model of diabetic neuropathic pain in rats. Male Wistar rats were made diabetic by a single intraperitoneal injection of streptozotocin (80 mg/kg). Sensitivity to mechanical and thermal stimuli was measured with the paw-pressure and hot-plate test, respectively. The formalin test was used to measure sensitivity to chemical stimuli. Diabetic animals with pain thresholds lower for at least 25% compared to the non-diabetic group were considered neuropathic and were injected with BTX-A either subcutaneously (3, 5 and 7 U/kg) or intrathecally (1 U/kg). Mechanical and thermal sensitivity was measured at several time-points. After peripheral application, BTX-A (5 and 7 U/kg) reduced mechanical and thermal hypersensitivity not only on ipsilateral, but on contralateral side, too. The antinociceptive effect started 5 days following BTX-A injection and lasted at least 15 days. Formalin-induced hypersensitivity in diabetic animals was abolished as well. When applied intrathecally, BTX-A (1 U/kg) reduced diabetic hyperalgesia within 24 h supporting the assumption of retrograde axonal transport of BTX-A from the peripheral site of injection to central nervous system. The results presented here demonstrate the long-lasting pain reduction after single BTX-A injection in the animals with diabetic neuropathy. The bilateral pain reduction after unilateral toxin application and the effectiveness of lower dose with the faster onset after the intrathecal injection suggest the involvement of the central nervous system in the antinociceptive action of BTX-A in painful diabetic neuropathy. (C) 2010 Elsevier B.V. All rights reserved.