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  1. Article ; Online: Cerebro-Cerebellar Networks in Migraine Symptoms and Headache.

    Noseda, Rodrigo

    Frontiers in pain research (Lausanne, Switzerland)

    2022  Volume 3, Page(s) 940923

    Abstract: The cerebellum is associated with the biology of migraine in a variety of ways. Clinically, symptoms such as fatigue, motor weakness, vertigo, dizziness, difficulty concentrating and finding words, nausea, and visual disturbances are common in different ... ...

    Abstract The cerebellum is associated with the biology of migraine in a variety of ways. Clinically, symptoms such as fatigue, motor weakness, vertigo, dizziness, difficulty concentrating and finding words, nausea, and visual disturbances are common in different types of migraine. The neural basis of these symptoms is complex, not completely known, and likely involve activation of both specific and shared circuits throughout the brain. Posterior circulation stroke, or neurosurgical removal of posterior fossa tumors, as well as anatomical tract tracing in animals, provided the first insights to theorize about cerebellar functions. Nowadays, with the addition of functional imaging, much progress has been done on cerebellar structure and function in health and disease, and, as a consequence, the theories refined. Accordingly, the cerebellum may be useful but not necessary for the execution of motor, sensory or cognitive tasks, but, rather, would participate as an efficiency facilitator of neurologic functions by improving speed and skill in performance of tasks produced by the cerebral area to which it is reciprocally connected. At the subcortical level, critical regions in these processes are the basal ganglia and thalamic nuclei. Altogether, a modulatory role of the cerebellum over multiple brain regions appears compelling, mainly by considering the complexity of its reciprocal connections to common neural networks involved in motor, vestibular, cognitive, affective, sensory, and autonomic processing-all functions affected at different phases and degrees across the migraine spectrum. Despite the many associations between cerebellum and migraine, it is not known whether this structure contributes to migraine initiation, symptoms generation or headache. Specific cerebellar dysfunction
    Language English
    Publishing date 2022-07-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2673-561X
    ISSN (online) 2673-561X
    DOI 10.3389/fpain.2022.940923
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Central generators of migraine and autonomic cephalalgias as targets for personalized pain management: Translational links.

    Noseda, Rodrigo / Villanueva, Luis

    European journal of pain (London, England)

    2023  Volume 27, Issue 9, Page(s) 1126–1138

    Abstract: Background and objective: Migraine oscillates between different states in association with internal homeostatic functions and biological rhythms that become more easily dysregulated in genetically susceptible individuals. Clinical and pre-clinical data ... ...

    Abstract Background and objective: Migraine oscillates between different states in association with internal homeostatic functions and biological rhythms that become more easily dysregulated in genetically susceptible individuals. Clinical and pre-clinical data on migraine pathophysiology support a primary role of the central nervous system (CNS) through 'dysexcitability' of certain brain networks, and a critical contribution of the peripheral sensory and autonomic signalling from the intracranial meningeal innervation. This review focuses on the most relevant back and forward translational studies devoted to the assessment of CNS dysfunctions involved in primary headaches and discusses the role they play in rendering the brain susceptible to headache states.
    Methods and results: We collected a body of scientific literature from human and animal investigations that provide a compelling perspective on the anatomical and functional underpinnings of the CNS in migraine and trigeminal autonomic cephalalgias. We focus on medullary, hypothalamic and corticofugal modulation mechanisms that represent strategic neural substrates for elucidating the links between trigeminovascular maladaptive states, migraine triggering and the temporal phenotype of the disease.
    Conclusion: It is argued that a better understanding of homeostatic dysfunctional states appears fundamental and may benefit the development of personalized therapeutic approaches for improving clinical outcomes in primary headache disorders.
    Significance: This review focuses on the most relevant back and forward translational studies showing the crucial role of top-down brain modulation in triggering and maintaining primary headache states and how these central dysfunctions may interact with personalized pain management strategies.
    MeSH term(s) Animals ; Humans ; Headache ; Migraine Disorders/therapy ; Pain ; Brain ; Trigeminal Autonomic Cephalalgias/therapy
    Language English
    Publishing date 2023-07-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1390424-3
    ISSN 1532-2149 ; 1090-3801
    ISSN (online) 1532-2149
    ISSN 1090-3801
    DOI 10.1002/ejp.2158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Unanswered questions in headache: so what is photophobia, anyway?

    Noseda, Rodrigo

    Headache

    2013  Volume 53, Issue 10, Page(s) 1679–1680

    MeSH term(s) Headache/diagnosis ; Headache/epidemiology ; Humans ; Light/adverse effects ; Nervous System Diseases/diagnosis ; Nervous System Diseases/epidemiology ; Photophobia/diagnosis ; Photophobia/epidemiology
    Language English
    Publishing date 2013-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 410130-3
    ISSN 1526-4610 ; 0017-8748
    ISSN (online) 1526-4610
    ISSN 0017-8748
    DOI 10.1111/head.12230
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Neurobiology of Photophobia.

    Burstein, Rami / Noseda, Rodrigo / Fulton, Anne B

    Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society

    2019  Volume 39, Issue 1, Page(s) 94–102

    Abstract: Background: Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways through which light information is processed have paved the way to a better ... ...

    Abstract Background: Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways through which light information is processed have paved the way to a better understanding of the neurobiology of photophobia and the complexity of the symptoms triggered by light.
    Purpose: The purpose of this review is to summarize recent anatomical and physiological studies on the neurobiology of photophobia with emphasis on migraine.
    Recent findings: Observations made in blind and seeing migraine patients, and in a variety of animal models, have led to the discovery of a novel retino-thalamo-cortical pathway that carries photic signal from melanopsinergic and nonmelanopsinergic retinal ganglion cells (RGCs) to thalamic neurons. Activity of these neurons is driven by migraine and their axonal projections convey signals about headache and light to multiple cortical areas involved in the generation of common migraine symptoms. Novel projections of RGCs into previously unidentified hypothalamic neurons that regulate parasympathetic and sympathetic functions have also been discovered. Finally, recent work has led to a novel understanding of color preference in migraine-type photophobia and of the roles played by the retina, thalamus, and cortex.
    Summary: The findings provide a neural substrate for understanding the complexity of aversion to light in patients with migraine and neuro-ophthalmologic other disorders.
    MeSH term(s) Animals ; Cerebral Cortex/physiopathology ; Humans ; Migraine Disorders/complications ; Migraine Disorders/physiopathology ; Neural Pathways/physiopathology ; Photophobia/etiology ; Photophobia/physiopathology ; Retinal Ganglion Cells/physiology ; Thalamus/physiopathology
    Language English
    Publishing date 2019-02-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1189901-3
    ISSN 1536-5166 ; 1070-8022
    ISSN (online) 1536-5166
    ISSN 1070-8022
    DOI 10.1097/WNO.0000000000000766
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Current understanding of photophobia, visual networks and headaches.

    Noseda, Rodrigo / Copenhagen, David / Burstein, Rami

    Cephalalgia : an international journal of headache

    2018  Volume 39, Issue 13, Page(s) 1623–1634

    Abstract: Objective: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders.: Background: Photophobia is a poorly understood light-induced ... ...

    Abstract Objective: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders.
    Background: Photophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the search for answers quite challenging. In the field of headaches, significant progress has been made recently on how specific visual networks contribute to photophobia features such as light-induced intensification of headache, increased perception of brightness and visual discomfort, which are frequently experienced by migraineurs. Such progress improved our understanding of the phenomenon and points to abnormal processing of light by both cone/rod-mediated image-forming and melanopsin-mediated non-image-forming visual pathways, and the consequential transfer of photic signals to multiple brain regions involved in sensory, autonomic and emotional regulation.
    Conclusion: Photophobia phenotype is diverse, and the relative contribution of visual, trigeminal and autonomic systems may depend on the disease it emerges from. In migraine, photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis, making its association with headache more complex than previously thought.
    MeSH term(s) Animals ; Blindness/physiopathology ; Brain Stem/physiopathology ; Color ; Headache/complications ; Headache/physiopathology ; Humans ; Light/adverse effects ; Mesencephalon/physiopathology ; Mice ; Migraine Disorders/complications ; Migraine Disorders/physiopathology ; Photic Stimulation/adverse effects ; Photophobia/etiology ; Photophobia/physiopathology ; Retinal Ganglion Cells/physiology ; Retinal Rod Photoreceptor Cells/physiology ; Retinal Rod Photoreceptor Cells/radiation effects ; Rod Opsins/physiology ; Somatosensory Cortex/physiopathology ; Thalamus/physiopathology ; Visual Pathways/physiopathology
    Chemical Substances Rod Opsins ; melanopsin
    Language English
    Publishing date 2018-06-25
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 604567-4
    ISSN 1468-2982 ; 0333-1024
    ISSN (online) 1468-2982
    ISSN 0333-1024
    DOI 10.1177/0333102418784750
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Current understanding of thalamic structure and function in migraine.

    Younis, Samaira / Hougaard, Anders / Noseda, Rodrigo / Ashina, Messoud

    Cephalalgia : an international journal of headache

    2018  Volume 39, Issue 13, Page(s) 1675–1682

    Abstract: Objective: To review and discuss the literature on the role of thalamic structure and function in migraine.: Discussion: The thalamus holds an important position in our understanding of allodynia, central sensitization and photophobia in migraine. ... ...

    Abstract Objective: To review and discuss the literature on the role of thalamic structure and function in migraine.
    Discussion: The thalamus holds an important position in our understanding of allodynia, central sensitization and photophobia in migraine. Structural and functional findings suggest abnormal functional connectivity between the thalamus and various cortical regions pointing towards an altered pain processing in migraine. Pharmacological nociceptive modulation suggests that the thalamus is a potential drug target.
    Conclusion: A critical role for the thalamus in migraine-related allodynia and photophobia is well established. Additionally, the thalamus is most likely involved in the dysfunctional pain modulation and processing in migraine, but further research is needed to clarify the exact clinical implications of these findings.
    MeSH term(s) Analgesics/pharmacology ; Analgesics/therapeutic use ; Brain Mapping ; Central Nervous System Sensitization/physiology ; Cerebral Cortex/physiopathology ; Connectome ; Emotions/physiology ; Humans ; Hyperalgesia/etiology ; Hyperalgesia/physiopathology ; Magnetic Resonance Imaging ; Migraine Disorders/complications ; Migraine Disorders/diagnostic imaging ; Migraine Disorders/pathology ; Migraine Disorders/physiopathology ; Neural Pathways/physiopathology ; Nociception/physiology ; Organ Size ; Pain Perception/physiology ; Photophobia/etiology ; Photophobia/physiopathology ; Positron-Emission Tomography ; Proton Magnetic Resonance Spectroscopy ; Thalamic Nuclei/physiopathology ; Thalamus/diagnostic imaging ; Thalamus/drug effects ; Thalamus/pathology ; Thalamus/physiopathology ; Tomography, X-Ray Computed
    Chemical Substances Analgesics
    Language English
    Publishing date 2018-08-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 604567-4
    ISSN 1468-2982 ; 0333-1024
    ISSN (online) 1468-2982
    ISSN 0333-1024
    DOI 10.1177/0333102418791595
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Neuropeptides and Neurotransmitters That Modulate Thalamo-Cortical Pathways Relevant to Migraine Headache.

    Noseda, Rodrigo / Borsook, David / Burstein, Rami

    Headache

    2017  Volume 57 Suppl 2, Page(s) 97–111

    Abstract: Dynamic thalamic regulation of sensory signals allows the cortex to adjust better to rapidly changing behavioral, physiological, and environmental demands. To fulfill this role, thalamic neurons must themselves be subjected to constantly changing ... ...

    Abstract Dynamic thalamic regulation of sensory signals allows the cortex to adjust better to rapidly changing behavioral, physiological, and environmental demands. To fulfill this role, thalamic neurons must themselves be subjected to constantly changing modulatory inputs that originate in multiple neurochemical pathways involved in autonomic, affective, and cognitive functions. This review defines a chemical framework for thinking about the complexity of factors that modulate the response properties of relay trigeminovascular thalamic neurons. Following the presentation of scientific evidence for monosynaptic connections between thalamic trigeminovascular neurons and axons containing glutamate, GABA, dopamine, noradrenaline, serotonin, histamine, orexin, and melanin-concentrating hormone, this review synthesizes a large body of data to propose that the transmission of headache-related nociceptive signals from the thalamus to the cortex is modulated by potentially opposing forces and that the so-called 'decision' of which system (neuropeptide/neurotransmitter) will dominate the firing of a trigeminovascular thalamic neuron at any given time is determined by the constantly changing physiological (sleep, wakefulness, food intake, body temperature, heart rate, blood pressure), behavioral (addiction, isolation), cognitive (attention, learning, memory use), and affective (stress, anxiety, depression, anger) adjustment needed to keep homeostasis.
    Language English
    Publishing date 2017-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 410130-3
    ISSN 1526-4610 ; 0017-8748
    ISSN (online) 1526-4610
    ISSN 0017-8748
    DOI 10.1111/head.13083
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain.

    Noseda, Rodrigo / Burstein, Rami

    Pain

    2013  Volume 154 Suppl 1

    Abstract: Scientific evidence support the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation and sensitization of the trigeminovascular pathway, and consequential ... ...

    Abstract Scientific evidence support the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. Data supporting the activation and sensitization of the trigeminovascular system include the progressive development of cephalic and whole-body cutaneous allodynia during a migraine attack. Also, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex.
    Language English
    Publishing date 2013-12-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1016/j.pain.2013.07.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain.

    Noseda, Rodrigo / Burstein, Rami

    Pain

    2013  Volume 154 Suppl 1, Page(s) S44–53

    Abstract: Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of the trigeminovascular pathway, and consequential ... ...

    Abstract Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory, and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. Data supporting the activation and sensitization of the trigeminovascular system include the progressive development of cephalic and whole-body cutaneous allodynia during a migraine attack. In addition, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex.
    MeSH term(s) Afferent Pathways/pathology ; Afferent Pathways/physiopathology ; Animals ; Brain/pathology ; Brain/physiopathology ; Cerebral Arteries/innervation ; Cerebral Arteries/physiopathology ; Cortical Spreading Depression ; Humans ; Migraine Disorders/physiopathology ; Models, Cardiovascular ; Models, Neurological ; Pain/pathology ; Pain/physiopathology ; Trigeminal Nerve/physiopathology
    Language English
    Publishing date 2013-07-25
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1016/j.pain.2013.07.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Non-Trigeminal Nociceptive Innervation of the Posterior Dura: Implications to Occipital Headache.

    Noseda, Rodrigo / Melo-Carrillo, Agustin / Nir, Rony-Reuven / Strassman, Andrew M / Burstein, Rami

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2019  Volume 39, Issue 10, Page(s) 1867–1880

    Abstract: Current understanding of the origin of occipital headache falls short of distinguishing between cause and effect. Most preclinical studies involving trigeminovascular neurons sample neurons that are responsive to stimulation of dural areas in the ... ...

    Abstract Current understanding of the origin of occipital headache falls short of distinguishing between cause and effect. Most preclinical studies involving trigeminovascular neurons sample neurons that are responsive to stimulation of dural areas in the anterior 2/3 of the cranium and the periorbital skin. Hypothesizing that occipital headache may involve activation of meningeal nociceptors that innervate the posterior ⅓ of the dura, we sought to map the origin and course of meningeal nociceptors that innervate the posterior dura overlying the cerebellum. Using AAV-GFP tracing and single-unit recording techniques in male rats, we found that neurons in C2-C3 DRGs innervate the dura of the posterior fossa; that nearly half originate in DRG neurons containing CGRP and TRPV1; that nerve bundles traverse suboccipital muscles before entering the cranium through bony canals and large foramens; that central neurons receiving nociceptive information from the posterior dura are located in C2-C4 spinal cord and that their cutaneous and muscle receptive fields are found around the ears, occipital skin and neck muscles; and that administration of inflammatory mediators to their dural receptive field, sensitize their responses to stimulation of the posterior dura, peri-occipital skin and neck muscles. These findings lend rationale for the common practice of attempting to alleviate migraine headaches by targeting the greater and lesser occipital nerves with anesthetics. The findings also raise the possibility that such procedures may be more beneficial for alleviating occipital than non-occipital headaches and that occipital migraines may be associated more closely with cerebellar abnormalities than in non-occipital migraines.
    MeSH term(s) Animals ; Cervical Cord/physiology ; Dura Mater/cytology ; Dura Mater/physiology ; Ganglia, Spinal/cytology ; Ganglia, Spinal/physiology ; Headache/physiopathology ; Male ; Neural Pathways/cytology ; Neural Pathways/physiology ; Neuroanatomical Tract-Tracing Techniques ; Neurons/cytology ; Neurons/physiology ; Nociceptors/physiology ; Rats, Sprague-Dawley
    Language English
    Publishing date 2019-01-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.2153-18.2018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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