Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications for migraine and other pains.
Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications for migraine and other pains.
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DOI：
10.1177/0333102414527648
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Brin MF
中科院分区：
文献类型：
--
作者：
Burstein R;Zhang X;Levy D;Aoki KR;Brin MF
脑膜和其他三叉神经伤害性感受器被认为在偏头痛的发生中起着重要作用。目前，唯一被批准的外周给药的慢性偏头痛预防药物是onabotulinumoxinA。本研究的目的是确定A型肉毒神经毒素(BONT-A)如何影响幼稚和敏感型脑膜伤害性感受器。我们用电生理技术识别了43C和36Aδ脑膜伤害性感受器，并测量了它们在注射BONT-A前后硬脑膜和颅外缝线感受区的自发放电和诱发放电。通常，BoNT-A抑制C-而不是A-δ-脑膜伤害性感受器。当应用于非敏化的C单位时，BoNT-A抑制了对机械刺激硬脑膜的反应。当应用于致敏单位时，BoNT-A逆转了机械超敏反应。当在致敏前应用时，BoNT-A可防止机械过敏的发展。当在颅外缝合脑膜伤害性感受器的分支时，BoNT-A抑制缝合分支的机械反应，但不抑制硬脑膜轴突。相反，BoNT-A并不抑制机械刺激硬脑膜的C单位反应，也不抑制其自发活动。这项研究为BoNT-A抑制外周三叉神经血管神经元机械伤害性感受的能力提供了证据。这些发现表明，BoNT-A通过阻止高阈值机械敏感离子通道与神经末梢膜的融合，干扰了与机械性疼痛有关的高阈值离子通道的神经元表面表达。
Meningeal and other trigeminal nociceptors are thought to play important roles in the initiation of migraine headache. Currently, the only approved peripherally administered chronic migraine prophylactic drug is onabotulinumtoxinA. The purpose of this study was to determine how botulinum neurotoxin type A (BoNT-A) affects naïve and sensitized meningeal nociceptors. Using electrophysiological techniques, we identified 43 C- and 36 Aδ-meningeal nociceptors, and measured their spontaneous and evoked firing before and after BoNT-A administration to intracranial dura and extracranial suture-receptive fields. As a rule, BoNT-A inhibited C- but not Aδ-meningeal nociceptors. When applied to nonsensitized C-units, BoNT-A inhibited responses to mechanical stimulation of the dura with suprathreshold forces. When applied to sensitized units, BoNT-A reversed mechanical hypersensitivity. When applied before sensitization, BoNT-A prevented development of mechanical hypersensitivity. When applied extracranially to suture branches of intracranial meningeal nociceptors, BoNT-A inhibited the mechanical responsiveness of the suture branch but not dural axon. In contrast, BoNT-A did not inhibit C-unit responses to mechanical stimulation of the dura with threshold forces, or their spontaneous activity. The study provides evidence for the ability of BoNT-A to inhibit mechanical nociception in peripheral trigeminovascular neurons. These findings suggest that BoNT-A interferes with neuronal surface expression of high-threshold mechanosensitive ion channels linked preferentially to mechanical pain by preventing their fusion into the nerve terminal membrane.
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影响因子：
3.7
作者：
Drew, Liam J.;Rugiero, Francois;Cesare, Paolo;Gale, Jonathan E.;Abrahamsen, Bjarke;Bowden, Sarah;Heinzmann, Sebastian;Robinson, Michelle;Brust, Andreas;Colless, Barbara;Lewis, Richard J.;Wood, John N.
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Wood, John N.
影响因子：
3.3
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通讯作者：
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影响因子：
2.5
作者：
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通讯作者：
Stucky, Cheryl L.
影响因子：
64.8
作者：
Coste, Bertrand;Xiao, Bailong;Santos, Jose S.;Syeda, Ruhma;Grandl, Joerg;Spencer, Kathryn S.;Kim, Sung Eun;Schmidt, Manuela;Mathur, Jayanti;Dubin, Adrienne E.;Montal, Mauricio;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem
影响因子：
7.4
作者：
Gazerani, Parisa;Staahl, Camilla;Arendt-Nielson, Lars
通讯作者：
Arendt-Nielson, Lars