Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy.

Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy.
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DOI:
10.1371/journal.pone.0029803
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Lacković Z
Lacković Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Filipović B;Matak I;Bach-Rojecky L;Lacković Z

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眶下神经收缩(IoNC)是三叉神经病变的实验模型。在这个模型中,我们研究了IoNC是否伴有硬脑膜外渗,以及A型肉毒毒素(BoNT/A)是否可以减轻疼痛和硬脑膜外渗。将3.5 U/kg的BoNT/A注射到振动垫中,观察14d后出现机械异常性痛的大鼠。用von Frey纤维测定异常性疼痛,用Evans蓝-血浆蛋白复合物比色吸收测定硬膜外渗。在口面部福尔马林引起的疼痛中也检查了硬脑膜外渗。单侧IoNC及福尔马林注射导致双侧硬脑膜外渗。单次单侧BoNT/A注射双侧可减少离子诱导的硬脑膜外渗,以及异常性疼痛(持续2周以上)。同样,BoNT/A减少了福尔马林引起的疼痛和硬脑膜外渗。BoNT/A对IoNC模型疼痛和硬脑膜外渗的影响依赖于通过感觉神经元的轴突运输,三叉神经节注射秋水仙碱(5 mM, 2µl)完全阻止BoNT/A的作用。两种不同类型的疼痛,离子型和福尔马林,伴随硬脑膜外渗。实验动物单侧注射BoNT/ a的持久效果表明BoNT/ a可能对与硬脑膜神经源性炎症相关的颅面疼痛具有长期有益作用。BoNT/A的双侧效应和对逆行轴突转运的依赖表明其作用的中心部位。
Infraorbital nerve constriction (IoNC) is an experimental model of trigeminal neuropathy. We investigated if IoNC is accompanied by dural extravasation and if botulinum toxin type A (BoNT/A) can reduce pain and dural extravasation in this model. Rats which developed mechanical allodynia 14 days after the IoNC were injected with BoNT/A (3.5 U/kg) into vibrissal pad. Allodynia was tested by von Frey filaments and dural extravasation was measured as colorimetric absorbance of Evans blue - plasma protein complexes. Presence of dural extravasation was also examined in orofacial formalin-induced pain. Unilateral IoNC, as well as formalin injection, produced bilateral dural extravasation. Single unilateral BoNT/A injection bilaterally reduced IoNC induced dural extravasation, as well as allodynia (lasting more than 2 weeks). Similarly, BoNT/A reduced formalin-induced pain and dural extravasation. Effects of BoNT/A on pain and dural extravasation in IoNC model were dependent on axonal transport through sensory neurons, as evidenced by colchicine injections (5 mM, 2 µl) into the trigeminal ganglion completely preventing BoNT/A effects. Two different types of pain, IoNC and formalin, are accompanied by dural extravasation. The lasting effect of a unilateral injection of BoNT/A in experimental animals suggests that BoNT/A might have a long-term beneficial effect in craniofacial pain associated with dural neurogenic inflammation. Bilateral effects of BoNT/A and dependence on retrograde axonal transport suggest a central site of its action.
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