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Magnetic Resonance Imaging (MRI) and immunohistochemical investigations of CNS activity in a novel preclinical migraine model

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MRI provides novel insight into migraine

Migraine pain is a global health problem with nearly 15 % of the European population suffering from migraines. Given the great socioeconomic implications, novel treatments are required.

Fundamental Research
Health

The cause of migraine is highly complex, involving multiple regions of the brain. This makes it difficult to obtain a complete understanding of the mechanisms underlying this condition. Available treatments are not very effective and are associated with a plethora of side effects. To address this, scientists of the EU-funded MRIGRAINE project proposed to use a novel preclinical model of migraine along with magnetic resonance imaging (MRI) to investigate altered activity in the central nervous system (CNS). The idea was to associate changes in CNS function with the development of migraine-like symptoms, and to identify the affected brain areas. The team generated a clinically-relevant model of migraine through continuous infusion of the drug sumatriptan. This elicited an increased response of neurons, a condition known as facial allodynia. The migraine-like state was further investigated by MRI and functional MRI to assess changes in resting state connectivity between experimental and control groups. Furthermore, this allowed the team to determine the differences in the magnitude and temporal dynamics of an evoked neuronal response for utility as a novel biomarker. Scientists discovered that on day 6 of sumatriptan administration, the cerebral blood flow in the grey matter structures was significantly reduced when compared to control animals. Consistent with data in humans suffering from migraine who are hyper-responsive and prone to aberrant cortical activity, researchers observed oscillations in the regions of the brain associated with pain pathways. Importantly, sumatriptan-treated animals show long-term altered neuronal connectivity over control animals following whisker pad or bright light stimulation. Immunohistochemical analysis demonstrated changes in expression of specific indicators of altered excitability, further validating the altered and prolonged central and peripheral changes seen by MRI. Collectively, the MRIGRAINE findings show that the functional MRI changes in this rodent model of migraine are similar to those observed in humans and correlate with the development of increased pain perception. Using this preclinical model of migraine, researchers also identified the affected brain regions, a finding that could be used to develop anti-migraine treatments with better efficacy and fewer side effects.

Keywords

MRI, migraine, MRIGRAINE, sumatriptan, preclinical model

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