Laboratory of Molecular Neuropharmacology, Department of Pharmacology and Croatian Brain Research Institute, University of Zagreb School of Medicine, Zagreb, Croatia.
PLoS One. 2012;7(1):e29803. doi: 10.1371/journal.pone.0029803. Epub 2012 Jan 4.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: 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.
眶下神经缩窄（IoNC）是一种三叉神经病变的实验模型。我们研究了 IoNC 是否伴有硬脑膜外渗，如果肉毒毒素 A（BoNT/A）可以减轻这种模型中的疼痛和硬脑膜外渗。
方法/主要发现：在 IoNC 后 14 天出现机械性痛觉过敏的大鼠，将 BoNT/A（3.5 U/kg）注入触须垫。通过 von Frey 纤维测试痛觉过敏，通过 Evans 蓝-血浆蛋白复合物的比色吸光度测量硬脑膜外渗。还在口腔福尔马林诱导性疼痛中检查了硬脑膜外渗的存在。单侧 IoNC 以及福尔马林注射均导致双侧硬脑膜外渗。单次单侧 BoNT/A 注射可双侧减少 IoNC 诱导的硬脑膜外渗以及痛觉过敏（持续超过 2 周）。同样，BoNT/A 可减轻福尔马林诱导的疼痛和硬脑膜外渗。BoNT/A 对 IoNC 模型中疼痛和硬脑膜外渗的作用依赖于感觉神经元的轴突运输，这一点通过向三叉神经节注射长春新碱（5mM，2µl）得到证实，该药物完全阻止了 BoNT/A 的作用。
结论/意义：两种不同类型的疼痛，IoNC 和福尔马林，均伴有硬脑膜外渗。在实验动物中，单侧 BoNT/A 注射的持久效果表明，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的有益作用。BoNT/A 的双侧作用和对逆行轴突运输的依赖性表明其作用部位位于中枢。
