Changes of Meningeal Excitability Mediated by Corticotrigeminal Networks: A Link for the Endogenous Modulation of Migraine Pain

Abstract

Alterations in cortical excitability are implicated in the pathophysiology of migraine. However, the relationship between cortical spreading depression (CSD) and headache has not been fully elucidated. We aimed to identify the corticofugal networks that directly influence meningeal nociception in the brainstem trigeminocervical complex (Sp5C) of the rat. Cortical areas projecting to the brainstem were first identified by retrograde tracing from Sp5C areas that receive direct meningeal inputs. Anterograde tracers were then injected into these cortical areas to determine the precise pattern of descending axonal terminal fields in the Sp5C. Descending cortical projections to brainstem areas innervated by the ophthalmic branch of the trigeminal nerve originate contralaterally from insular (Ins) and primary somatosensory (S1) cortices and terminate in laminae I-II and III-V of the Sp5C, respectively. In another set of experiments, electrophysiological recordings were simultaneously performed in Ins, S1 or primary visual cortex (V1), and Sp5C neurons. KCl was microinjected into such cortical areas to test the effects of CSD on meningeal nociception. CSD initiated in Ins and S1 induced facilitation and inhibition of meningeal-evoked responses, respectively. CSD triggered in V1 affects differently Ins and S1 cortices, enhancing or inhibiting meningeal-evoked responses of Sp5C, without affecting cutaneous-evoked nociceptive responses. Our data suggest that "top-down" influences from lateralized areas within Ins and S1 selectively affect interoceptive (meningeal) over exteroceptive (cutaneous) nociceptive inputs onto Sp5C. Such corticofugal influences could contribute to the development of migraine pain in terms of both topographic localization and pain tuning during an attack.

A Novel Visual Psychometric Test for Light-Induced Discomfort Using Red and Blue Light Stimuli Under Binocular and Monocular Viewing Conditions

“…1,[9][10][11][12][13][14][15][16] This is supported by several lines of evidence. First, animal studies report light-aversive behaviors in neonatal rodents before rod/cone development, but an absence of these behaviors in melanopsin knockout mice.…”

“…23 Fourth, ipRGCs project directly to pain centers in the posterior thalamus where afferent retinal inputs converge with the trigeminal nociceptive pathway. 9,10 Collectively, there is accumulating evidence showing that the ipRGC pathway is the primary transducer of photophobia.…”

Association between Cervical Spondylosis and Migraine: A Nationwide Retrospective Cohort Study

“…In addition, several studies have reported that myofascial trigger points could reproduce migraine symptoms 37,38 , Moreover, an increasing amount of evidence shows that dyscoordination between the dorsal horns of the upper cervical spinal cord and trigeminal nucleus caudalis may induce cervicogenic headaches. The prolonged irritated inputs implicate in the pain processing through trigeminovascular system, which can provoke and worsen the symptoms of migraine 39,40 .…”

Cortical spreading depression and central pain networks in trigeminal nuclei modulation: time for an integrated migraine pathogenesis perspective

“…Although this study raised deep criticism for a possible suboptimal study design [33], two direct anatomical topdown projections to trigeminal nuclei have been very recently described [34]. The first, associated with facilitatory effects, directly links a specific insula area to trigeminovascular neurons located in I and II laminae.…”