Spreading depolarization, usually termed cortical spreading depression has been proposed as the pathophysiological substrate of migraine aura and as an endogenous trigger of headache pain. The links between neurovascular coupling and cortical craniofacial nociceptive activities modulated by SD were assessed by combining in vivo local field potential (LFP) recordings in the primary somatosensory cortex (S1) with functional ultrasound imaging of S1 and caudal insular (INS) cortices of anesthetized male rats. A single SD wave triggered in the primary visual cortex elicited an ipsilateral, quadriphasic hemodynamic and electrophysiological response in S1 with an early phase consisting of concomitant increases of relative cerebral blood volume (rCBV) and LFPs. A transient hypoperfusion was then correlated with the beginning of the neuronal silence, followed by a strong increase of rCBV, whereas synaptic activities remained inhibited.

LFPs and rCBV recovery period was followed by a progressive increase in S1 and INS baseline activities and facilitation of cortical responses evoked by periorbital cutaneous receptive field stimulation. Sensitization of cortical ophthalmic fields by SD was bilateral, occurred with precise spatiotemporal profiles, and was significantly reduced by pretreatment with an NMDA antagonist. Combined high-resolution assessing of neurovascular coupling and electrophysiological activities has revealed a useful preclinical tool for deciphering central sensitization mechanisms involved in migraine attacks.

SIGNIFICANCE STATEMENT A crucial unsolved issue is whether visual aura and migraine headache are parallel or sequential processes. Here, we show that a single spreading depolarization wave triggered from the primary visual cortex is powerful enough to elicit progressive, sustained increases of hemodynamic and sensory responses to percutaneous periorbital noxious stimuli recorded in S1 and insular ophthalmic fields. Sensitization of cortical ophthalmic fields by SD was bilateral, occurred with precise spatiotemporal profiles, and was significantly reduced by pretreatment with an NMDA antagonist. Combined high-resolution assessing of neurovascular coupling and electrophysiological activities has revealed a useful preclinical tool for deciphering central sensitization mechanisms involved in migraine attacks.

扩散去极化，通常称为皮质扩散抑制，已被提议作为偏头痛先兆的病理生理学底物和头痛的内源性触发因素。通过结合体内评估神经血管耦合与 SD 调节的皮质颅面伤害性活动之间的联系初级体感皮层 (S1) 中的局部场电位 (LFP) 记录以及麻醉雄性大鼠的 S1 和尾岛 (INS) 皮质的功能性超声成像。在初级视觉皮层中触发的单个 SD 波在 S1 中引起同侧、四相血流动力学和电生理反应，早期阶段包括相对脑血容量 (rCBV) 和 LFP 的伴随增加。然后，短暂的低灌注与神经元沉默的开始相关，随后 rCBV 强烈增加，而突触活动仍然受到抑制。

LFPs 和 rCBV 恢复期之后是 S1 和 INS 基线活动的逐渐增加以及眶周皮肤感受野刺激引起的皮质反应的促进。SD 对皮质眼科区域的致敏是双侧的，发生时具有精确的时空分布，并且通过 NMDA 拮抗剂预处理显着降低。神经血管耦合和电生理活动的联合高分辨率评估揭示了一种有用的临床前工具，用于破译与偏头痛发作有关的中枢敏化机制。

意义声明一个尚未解决的关键问题是视觉先兆和偏头痛是平行的还是顺序的过程。在这里，我们表明从初级视觉皮层触发的单个扩散去极化波足够强大，足以引起对 S1 和岛叶眼野中记录的经皮眶周伤害性刺激的血液动力学和感觉反应的渐进、持续增加。SD 对皮质眼科区域的致敏是双侧的，发生时具有精确的时空分布，并且通过 NMDA 拮抗剂预处理显着降低。神经血管耦合和电生理活动的联合高分辨率评估揭示了一种有用的临床前工具，用于破译与偏头痛发作有关的中枢敏化机制。