OnabotulinumtoxinA (BoNT-A) is an Food and Drug Administration-approved, peripherally acting preventive migraine drug capable of inhibiting meningeal nociceptors. Expanding our view of how else this neurotoxin attenuates the activation of the meningeal nociceptors, we reasoned that if the stimulus that triggers the activation of the nociceptor is lessened, the magnitude and/or duration of the nociceptors' activation could diminish as well. In the current study, we further examine this possibility using electrocorticogram recording techniques, immunohistochemistry, and 2-photon microscopy. We report (1) that scalp (head) but not lumbar (back) injections of BoNT-A shorten the period of profound depression of spontaneous cortical activity that follows a pinprick-induced cortical spreading depression (CSD); (2) that neither scalp nor lumbar injections prevent the induction, occurrence, propagation, or spreading velocity of a single wave of CSD; (3) that cleaved SNAP25-one of the most convincing tools to determine the anatomical targeting of BoNT-A treatment-could easily be detected in pericranial muscles at the injection sites and in nerve fibers of the intracranial dura, but not within any cortical area affected by the CSD; (4) that the absence of cleaved SNAP25 within the cortex and pia is unrelated to whether the blood-brain barrier is intact or compromised; and (5) that BoNT-A does not alter vascular responses to CSD. To the best of our knowledge, this is the first report of peripherally applied BoNT-A's ability to alter a neuronal function along a central nervous system pathway involved in the pathophysiology of migraine.

中文翻译：

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OnabotulinumtoxinA 影响血脑屏障受损大鼠的皮质恢复期，但不影响皮质扩散抑制的发生或传播。

OnabotulinumtoxinA (BoNT-A) 是一种经美国食品和药物管理局批准的外周作用预防性偏头痛药物，能够抑制脑膜伤害感受器。扩大我们对这种神经毒素如何减弱脑膜伤害感受器激活的看法，我们推断，如果触发伤害感受器激活的刺激减少，伤害感受器激活的幅度和/或持续时间也会减少。在当前的研究中，我们使用皮质电图记录技术、免疫组织化学和双光子显微镜进一步研究了这种可能性。我们报告（1）头皮（头部）而不是腰部（背部）注射 BoNT-A 可以缩短针刺诱发的皮质扩散抑制（CSD）后自发皮质活动的深度抑制期；(2) 头皮或腰部注射均不能阻止单波 CSD 的诱发、发生、传播或传播速度；(3) SNAP25 的裂解是确定 BoNT-A 治疗的解剖靶点的最有说服力的工具之一，可以很容易地在注射部位的颅周肌肉和颅内硬脑膜的神经纤维中检测到，但在任何皮质区域内都检测不到受惩教署影响；(4) 皮质和软脑膜内不存在裂解的 SNAP25 与血脑屏障是否完整或受损无关；(5) BoNT-A 不会改变血管对 CSD 的反应。据我们所知，这是首次报道外周应用 BoNT-A 能够改变偏头痛病理生理学中枢神经系统通路的神经元功能。