Botulinum neurotoxin type A (BoNTA) decreases the mechanical sensitivity of nociceptors and inhibits neurogenic vasodilation in a craniofacial muscle targeted for migraine prophylaxis
Botulinum neurotoxin type A (BoNTA) decreases the mechanical sensitivity of nociceptors and inhibits neurogenic vasodilation in a craniofacial muscle targeted for migraine prophylaxis
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DOI：
10.1016/j.pain.2010.07.029
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发表时间：
2010-12-01
期刊：
影响因子：
7.4
通讯作者：
Cairns, Brian E.
中科院分区：
文献类型：
--
作者：
Gazerani, Parisa;Au, Sammy;Cairns, Brian E.
颅面肌肌肉注射 BoNTA 减少偏头痛的机制尚不清楚。在一项双盲研究中，研究了 BoNTA 对雌性大鼠个体颞肌伤害感受器的机械和化学反应性以及肌肉神经源性血管舒张的影响。肌内注射 BoNTA 或载体后 3 小时测量机械阈值，随后注射藻原谷氨酸后测量 10 分钟。注射 BoNTA 显着增加肌肉伤害感受器的机械阈值，而不改变肌肉表面温度，并阻断谷氨酸诱导的机械敏化和神经源性血管舒张。泮库溴铵引起的肌肉麻痹没有重现这些效应。颞肌的蛋白质印迹分析表明 BoNTA 显着降低 SNAP-25。使用谷氨酸生物传感器测量间质谷氨酸浓度表明，BoNTA 显着降低了谷氨酸浓度。肌肉伤害感受器的机械敏感性通过激活外周 NMDA 受体而受到谷氨酸浓度的调节。进行了免疫组织化学实验，结果表明一半表达 NMDA 的颞神经纤维共表达 P 物质或 CGRP。其他电生理学实验检查了 NMDA、CGRP 和 NK1 受体拮抗剂对谷氨酸诱导作用的影响。谷氨酸诱导的机械敏化仅被 NMDA 受体拮抗剂阻断，但肌肉神经源性血管舒张被 NMDA 或 CGRP 受体拮抗剂减弱。这些数据表明，将BoNTA注射到颅面肌中可以通过抑制谷氨酸释放而快速降低颞肌伤害性感受器的机械敏感性以及通过减弱肌肉伤害性感受器引发的CGRP释放来减轻偏头痛。 (C) 2010 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
The mechanism by which intramuscular injection of BoNTA into the craniofacial muscles decreases migraine headaches is not known. In a blinded study, the effect of BoNTA on the mechanical and chemical responsiveness of individual temporalis muscle nociceptors and muscle neurogenic vasodilation was investigated in female rats. Mechanical threshold was measured for 3 h following intramuscular injection of BoNTA or vehicle, and for 10 min after a subsequent injection of the algogen glutamate. Injection of BoNTA significantly increased the mechanical threshold of muscle nociceptors without altering the muscle surface temperature and blocked glutamate-induced mechanical sensitization and neurogenic vasodilation. None of these effects were reproduced by pancuronium-induced muscle paralysis. Western blot analysis of temporalis muscles indicated that BoNTA significantly decreased SNAP-25. Measurement of interstitial glutamate concentration with a glutamate biosensor indicated that BoNTA significantly reduced glutamate concentrations. The mechanical sensitivity of muscle nociceptors is modulated by glutamate concentration through activation of peripheral NMDA receptors. Immunohistochemical experiments were conducted and they indicated that half of the NMDA-expressing temporalis nerve fibers co-expressed substance P or CGRP. Additional electrophysiology experiments examined the effect of antagonists for NMDA, CGRP and NK1 receptors on glutamate-induced effects. Glutamate-induced mechanical sensitization was only blocked by the NMDA receptor antagonist, but muscle neurogenic vasodilation was attenuated by NMDA or CGRP receptor antagonists. These data suggest that injection of BoNTA into craniofacial muscles acts to decrease migraine headaches by rapidly decreasing the mechanical sensitivity of temporalis muscle nociceptors through inhibition of glutamate release and by attenuating the provoked release of CGRP from muscle nociceptors. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.