By Rodrigo Noseda, Carolyn A. Bernstein, Rony-Reuven Nir, Alice J. Lee, Anne B. Fulton, Suzanne M. Bertisch, Alexandra Hovaguimian, Dean M. Cestari, Rodrigo Saavedra-Walker, David Borsook, Bruce L. Doran, Catherine Buettner, and Rami Burstein | Brain | May 17, 2016

Abstract:

Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients’ experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.

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By Mohammad Sohail Asghar, Lino Becerra, Henrik B. W. Larsson, David Borsook, and Messoud Ashina | PLoS ONE | March 18, 2016

Abstract: 

Background

Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded blood-oxygenation-level-dependent (BOLD) signals in the brain by functional MRI after infusion of CGRP in a double-blind placebo-controlled crossover study of 27 healthy volunteers. BOLD-signals were recorded in response to noxious heat stimuli in the V1-area of the trigeminal nerve. In addition, we measured BOLD-signals after injection of sumatriptan (5-HT_1B/1D antagonist).

Results

Brain activation to noxious heat stimuli following CGRP infusion compared to baseline resulted in increased BOLD-signal in insula and brainstem, and decreased BOLD-signal in the caudate nuclei, thalamus and cingulate cortex. Sumatriptan injection reversed these changes.

Conclusion

The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli.

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By Lino Becerra, James Bishop, Gabi Barmettler, Jennifer Yanhua Xie, Edita Navratilova, Frank Porreca, and David Borsook | Journal of Neurophysiology | October 21, 2015

Abstract:

A number of drugs, including triptans, promote migraine chronification in susceptible individuals. In rats, a period of triptan administration over 7 days can produce “latent sensitization” (14 days after discontinuation of drug) demonstrated as enhanced sensitivity to presumed migraine triggers such as environmental stress and lowered threshold for electrically induced cortical spreading depression (CSD). Here, we have used fMRI to evaluate the early changes in brain networks at day 7 of sumatriptan administration that may induce latent sensitization as well as the potential response to stress. Following continuous infusion of sumatriptan, rats were scanned to measure changes in resting state networks and the response to bright light environmental stress. Rats receiving sumatriptan, but not saline infusion, showed significant differences in default mode, autonomic, basal ganglia, salience, and sensorimotor networks. Bright light stress produced CSD-like responses in sumatriptan treated but not control rats. Our data show the first brain related changes in a rat model of medication overuse headache and suggest that this approach could be used to evaluate the multiple brain networks involved that may promote this condition.

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By David Borsook, Rosanna Veggeberg, Nathalie Erpelding, Ronald Borra, Clas Linnman, Rami Burstein, and Lino Becerra | The Neuroscientist | August 19, 2015

Abstract:

The insula, a “cortical hub” buried within the lateral sulcus, is involved in a number of processes including goal-directed cognition, conscious awareness, autonomic regulation, interoception, and somatosensation. While some of these processes are well known in the clinical presentation of migraine (i.e., autonomic and somatosensory alterations), other more complex behaviors in migraine, such as conscious awareness and error detection, are less well described. Since the insula processes and relays afferent inputs from brain areas involved in these functions to areas involved in higher cortical function such as frontal, temporal, and parietal regions, it may be implicated as a brain region that translates the signals of altered internal milieu in migraine, along with other chronic pain conditions, through the insula into complex behaviors. Here we review how the insula function and structure is altered in migraine. As a brain region of a number of brain functions, it may serve as a model to study new potential clinical perspectives for migraine treatment.

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By David Borsook and David W. Dodick | Neurology | August 2015

Summary:

Migraine is a disease that contributes to major disability. Perhaps because migraine attacks are not immediately life-threatening per se and individuals return to a “normal” state between attacks, it is not taken seriously. However, migraine is associated with a number of comorbidities, including psychiatric disease, stroke, and other chronic pain disorders. Current acute treatments for episodic migraine are relatively effective, but preventive treatments for episodic and chronic migraine are far less so. Recent functional imaging studies have shown that the disease affects brain function and structure (either as a result of its genetic predisposition or as a result of repeated attacks). The current evidence in the pain field is that changes observed in brain function and structure may be reversible, adding credence to the notion that treating the disease aggressively and early may be beneficial to patients. Here we suggest a change in our approach to a disease that is currently not treated with the urgency that it deserves given its global prevalence, disease burden, and effects on brain function.

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