Neurobiology of Migraine

Headache Group, Department of Neurology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0114, USA.
Neuroscience (Impact Factor: 3.36). 04/2009; 161(2):327-41. DOI: 10.1016/j.neuroscience.2009.03.019
Source: PubMed


Migraine is a complex disorder of the brain whose mechanisms are only now being unraveled. It is common, disabling and economically costly. The pain suggests an important role of the nociceptive activation, or the perception of activation, of trigeminal cranial, particularly intracranial afferents. Moreover, the involvement of a multi-sensory disturbance that includes light, sound and smells, as well as nausea, suggests the problem may involve central modulation of afferent traffic more broadly. Brain imaging studies in migraine point to the importance of sub-cortical structures in the underlying pathophysiology of the disorder. Migraine may thus be considered an inherited dysfunction of sensory modulatory networks with the dominant disturbance affecting abnormal processing of essentially normal neural traffic.

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Available from: Anna P Andreou, May 07, 2014
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    • "The change in arterial diameter in response to electrical stimulation within trigeminal tissues as well as intravenous infusion served as an index of activation. This site was chosen due to the relevance for the neurobiology of headache (Goadsby et al., 2009). "
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    ABSTRACT: Activity within the CNS can be quantified by a variety of methods. Here, we present an indirect method utilizing the neuro-vascular coupling via a continuous measurement of the vessel diameter. In anaesthetized rats, induced neuronal activity in the trigeminal system could be detected via arterial diameter measurements at the back of the medullary brainstem. Building upon the previously described diameter plugin, in images aligned to compensate for ventilation and heart-rate associated movement, automated processing allowed an evaluation immediately after acquisition. Electrical stimulation of facial trigeminal areas or the cranial dura mater caused vasodilatation of arteries in the dorsal medullary brainstem, which was abolished after application of the CGRP receptor antagonist olcegepant. No change in diameter was observed in corresponding veins. Intravenous infusion of sodium sulfide, which induces nitroxyl formation, also induced vasodilatation of brainstem-supplying arteries. Both experiments show a functional role of CGRP in the trigeminal nuclear brainstem complex. The presented method allows estimating central activity at the spinal level by vascular responses.
    Full-text · Article · Dec 2015 · Brain research
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    • "The concept of blocking CGRP signaling for migraine prevention is very promising. It is generally believed that migraine is associated with disturbances in brain function, including the brainstem (Charles, 2012, 2013; Goadsby et al., 2009; Hargreaves and Shepheard, 1999). In patients, imaging techniques have demonstrated migraine-active regions in the brainstem including the midbrain, pons, substantia nigra, red nucleus, and periaqueductal gray (PAG) (Afridi et al., 2005a; Diener, 1997; Lakhan et al., 2013; Stankewitz et al., 2011; Weiller et al., 1995). "
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    ABSTRACT: Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus and spinal trigeminal nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, motor trigeminal nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Jun 2015 · The Journal of Comparative Neurology
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    • "CM is currently considered as a disorder of the central nervous system (Goadsby and Sprenger, 2010) that leads to structural, functional and pharmacological changes in the brain of affected subjects (Mathew, 2011). Occipital nerve stimulation (ONS) for refractory CM takes advantage of the functional continuum of the trigeminal nucleus into the dorsal horn of the high cervical region to neuromodulate, in a retrograde fashion, the trigeminocervical complex (Bartsch and Goadsby, 2003; Goadsby et al., 2009; Ellens and Levy, 2011). Case series show occipital nerve stimulation to be efficacious for the treatment of several headache disorders including migraine headaches, cluster headache, hemicrania continua and occipital neuralgia (Ellens and Levy, 2011). "
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    ABSTRACT: Funding sources Nevro Corp (Menlo Park, CA, USA) provided the HF10 SCS devices free of charge and funded the independent external statistical support. Conflicts of interest In relation to the content of this paper, RA received travel grants from Medtronic, Bos-ton Scientific and Nevro Corp, and consulting fees from St Jude Medical; SP received speaker fees and/or sponsorships to attend professional meetings from Nevro Corp and Medtronic; TS received consultancy fees and sponsorship to attend professional meetings from Nevro Corp and from Allergan; AA received travel sponsorship and speaker fees from Medtronic and Nevro Corp, and he is the principal investigator in separate studies sponsored by Medtronic and Nevro Corp; PM received travel grants, consultation fees, educational grants or advisory board reimbursement from Electrocore, Nevro Corp, St Jude Medical and Medtronic. VV, MM, ST and MRDF declared no conflict of interest. Abstract Background: A significant minority of chronic migraine (CM) subjects fail conventional medical treatment (rCM), becoming highly disabled. Implantation of an occipital nerve stimulator is a therapeutic option for these subjects. Paresthesia-free cervical 10 kHz spinal cord stimulation (HF10 SCS) may provide an alternative. We report the results of a prospective, open-label, exploratory study assessing the long-term safety, tolerability and efficacy of cervical HF10 SCS in cohort of rCM subjects. Methods: Included subjects were diagnosed with CM by an experienced headache specialist with the aid of an hourly headache diary. They were refractory to conventional medical treatments including onabotulinumtoxin-A injections. Medication overuse headache was not an exclusion criteria. Enrolled subjects underwent a 2-to 4-week tunnelled cervical HF10 SCS trial followed by a permanent system implant if a significant, subjective reduction in headache intensity/episodes was reported during the trial. Subjects were evaluated at baseline and 6 months after implantation with the aid of monthly diaries and headache-specific questionnaires. Results: Seventeen subjects underwent a trial of cervical HF10 SCS; 14 were still implanted at 6 months (one trial failure, one trial infection, one implant site infection). Seven of the 14 subjects had >30% reduction in headache days. The average reduction in headache days was 6.9 for the overall population and 12.9 among the responders. Three subjects reported tenderness over the IPG/connection site, and one had a lead migration that required surgical revision. Conclusion: Paresthesia-free cervical HF10 SCS may be a safe and effective therapeutic option for chronic migraineurs refractory to conventional treatments.
    Full-text · Article · Mar 2015 · European Journal of Pain
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