Altered Cortical Trigeminal Fields Excitability by Spreading Depolarization Revealed with in Vivo Functional...

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.