RESUMO
Spreading depolarization (SD), 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 (LFPs) recordings in the primary somatosensory cortex (S1) with functional ultrasound (fUS) 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 while 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 fields stimulation. Sensitization of cortical ophthalmic fields by SD was bilateral, occurred with precise spatiotemporal profiles and was significantly reduced by pre-treatment with a 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 STATEMENTA crucial unsolved issue is whether visual aura and migraine headache are parallel or sequential processes. Here we show that a single spreading depolarization (SD) 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 pre-treatment with a 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.
RESUMO
A large body of clinical and pre-clinical evidence has shown complex interactions between bottom-up and top-down mechanisms that are essential for the discrimination of noxious information and pain perception. These endogenous systems, mainly originating from the brainstem, hypothalamus and cerebral cortex, are strongly influenced by behavioral, cognitive and emotional factors that are relevant for the survival of the individual. Under pathological conditions, however, dysfunctional engagement of these descending pathways certainly contributes to the transformation from acute into chronic pain states. In disorders such as primary headaches, dysfunctions affecting brain regulation mechanisms contribute to the generation of episodic painful states in susceptible individuals, and to the evolution from acute to chronic migraine or cluster headache. Taken together, these studies support the concept that CNS mechanisms that process trigemino-vascular pain do not consist only of a bottom-up process, whereby a painful focus modifies the inputs to the next higher level. Indeed, several CNS regions mediate subtle forms of plasticity by adjusting neural maps downstream and, consequently, altering all the modulatory mechanisms as a result of sensory, autonomic, endocrine, cognitive and emotional influences. Disturbances in normal sensory processing within these loops could lead to maladaptive changes and impaired craniofacial functions at the origin of primary headaches.