Antinociceptive effect of Brazilian armed spider venom toxin Tx3-3 in animal models of neuropathic pain
Antinociceptive effect of Brazilian armed spider venom toxin Tx3-3 in animal models of neuropathic pain
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DOI：
10.1016/j.pain.2011.04.015
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发表时间：
2011-10-01
期刊：
影响因子：
7.4
通讯作者：
Ferreira, Juliano
中科院分区：
文献类型：
--
作者：
Dalmolin, Gerusa Duarte;Silva, Cassia Regina;Ferreira, Juliano
毒液肽为治疗疼痛的药物开发提供了特殊的来源。在这项研究中，我们研究了Tx 3 -3，从Phoneutria nigriventer毒液中分离的肽毒素，抑制高电压依赖性钙通道（VDCC），优先P/Q和R型VDCC的抗伤害性和副作用。我们测试了Tx 3 -3在伤害性（甩尾试验）、神经性（部分坐骨神经结扎和链脲佐菌素诱导的糖尿病性神经病变）和炎性（足底完全弗氏佐剂）疼痛的动物模型中的作用。在甩尾试验中，鞘内（i.t.）和脑室内（i. c. v.）在小鼠中注射Tx 3 -3引起了短暂的持续作用（对于i.t.，ED 50和95%置信区间为8.8 [4.1-18.8]和3.7 [1.6-8.4] pmol/位点）。和i. c. v.注射），而不损害运动功能，至少以高于有效剂量10-30倍的剂量。相比之下，X-芋螺毒素MVIIC，一种来自大芋螺毒液的P/Q和N-型VDCC阻断剂，在接近有效剂量的剂量下在甩尾试验中引起显著的运动障碍。Tx 3 -3在神经病理性疼痛模型中显示出持久的抗伤害性作用。鞘内注射Tx 3 -3（30 pmol/部位）可减轻小鼠坐骨神经损伤产生的机械性异常性疼痛以及链脲佐菌素诱导的小鼠和大鼠异常性疼痛。另一方面，i. t。注射Tx 3 -3不改变炎性疼痛。两者合计，我们的数据表明，Tx 3 -3显示普遍的抗伤害性作用，在神经性疼痛模型，并没有引起不良的运动效应，在抗伤害性有效剂量，这表明这种肽毒素持有作为一种新的治疗剂的控制神经性疼痛的希望。(C)2011年国际疼痛研究协会。由Elsevier B出版。版权所有© 2016
Venoms peptides have produced exceptional sources for drug development to treat pain. In this study we examined the antinociceptive and side effects of Tx3-3, a peptide toxin isolated from Phoneutria nigriventer venom, which inhibits high-voltage-dependent calcium channels (VDCC), preferentially P/Q and R-type VDCC. We tested the effects of Tx3-3 in animal models of nociceptive (tail-flick test), neuropathic (partial sciatic nerve ligation and streptozotocin-induced diabetic neuropathy), and inflammatory (intraplantar complete Freund's adjuvant) pain. In the tail-flick test, both intrathecal (i.t.) and intracerebroventricular (i.c.v.) injection of Tx3-3 in mice caused a short-lasting effect (ED50 and 95% confidence intervals of 8.8 [4.1-18.8] and 3.7 [1.6-8.4] pmol/site for i.t. and i.c.v. injection, respectively), without impairing motor functions, at least at doses 10-30 times higher than the effective dose. By comparison, x-conotoxin MVIIC, a P/Q and N-type VDCC blocker derived from Conus magus venom, caused significant motor impairment at doses close to efficacious dose in tail flick test. Tx3-3 showed a long-lasting antinociceptive effect in neuropathic pain models. Intrathecal injection of Tx3-3 (30 pmol/site) decreased both mechanical allodynia produced by sciatic nerve injury in mice and streptozotocin-induced allodynia in mice and rats. On the other hand, i.t. injection of Tx3-3 did not alter inflammatory pain. Taken together, our data show that Tx3-3 shows prevalent antinociceptive effects in the neuropathic pain models and does not cause adverse motor effects at antinociceptive efficacious doses, suggesting that this peptide toxin holds promise as a novel therapeutic agent for the control of neuropathic pain. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.