Neurobiology in primary headaches

Edvinsson, Lars; Uddman, Rolf

doi:10.1016/j.brainresrev.2004.09.007

Cited by 212 publications

(215 citation statements)

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“…The disorder is being recognized as a fundamental neurological problem, although the primary cause of migraine attacks is still unknown (Goadsby, 2005). There has been intense research to identify signal molecules in nociceptive fibers and modulator systems associated with the trigeminal system (Edvinsson and Uddman, 2005). Signal molecules such as substance P (SP), neuropeptide Y, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) have been studied but the only neuronal messenger so far reliably demonstrated in acute migraine attacks is the neuropeptide calcitonin gene-related peptide (CGRP) (Goadsby et al, 1988, Durham, 2006, Edvinsson and Goadsby, 2010.…”

Section: Introductionmentioning

confidence: 99%

Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

et al. 2010

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"Differential distribution of calcitonin gene-related peptide (CGRP) and CGRP receptor components (CLR and RAMP1) in the human trigeminal ganglion."Neuroscience, 2010, Jun 2 http://dx.doi.org/10.1016/j.neuroscience.2010.05.016Access to the published version may require journal subscription.Published with permission from: Elsevier Antibodies against purified CLR and RAMP1 proteins were produced and characterized for this study. Trigeminal ganglia were obtained at autopsy from adult subjects and sections from rat trigeminal ganglia were used to compare the immunostaining pattern. The number of cells expressing CGRP, CLR and RAMP1, respectively, were counted. In addition, the glial cells of trigeminal ganglion, particularly the satellite glial cell, were studied to understand a possible relation.We observed immunoreactivity for CGRP, CLR and RAMP1, in the human trigeminal ganglion: 49% of the neurons expressed CGRP, 37% CLR and 36% RAMP1. Co-localization of CGRP and the receptor components was rarely found. There were no CGRP immunoreactions in the glial cells; however some of the glial cells displayed CLR and RAMP1 immunoreactivity. Similar results were observed in rat trigeminal ganglia.We report that human and rat trigeminal neurons store CGRP, CLR and RAMP1, however, CGRP and CLR/RAMP1 do not co-localize regularly but are found in separate neurons. Glial cells also contain the CGRP receptor components but not CGRP. Our results indicate, for the first time, the possibility of CGRP signaling in the human trigeminal ganglion involving both neurons and satellite glial cells. This suggests a possible site of action for the novel CGRP receptor antagonists in migraine therapy.

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Section: Introductionmentioning

confidence: 99%

Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

et al. 2010

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“…These vessels are supplied with sympathetic, parasympathetic and sensory nerve fibres (Edvinsson and Uddman, 2005). Intense activation of trigeminal pain pathways in cluster headache and migraine may initiate parasympathetic reflexes in the superior salivatory nucleus, resulting in the release of the vasodilator vasoactive intestinal polypeptide and the manifestation of facial symptoms such as ipsilateral flushing and lacrimation (Edvinsson and Uddman, 2005;Knight, 2005). In the extreme, the intracranial vasodilatation evoked by these reflexes may compress sympathetic vasoconstrictor fibres that travel with the internal carotid artery through the carotid canal, ultimately releasing sympathetic vasoconstrictor tone and aggravating vasodilatation.…”

Section: The Trigeminovascular System In Migrainementioning

confidence: 99%

“…Similarly, Edvinsson and Uddman (2005) suggested that the trigeminovascular vasodilator reflex is, in part, generated via CGRP and VIP to offset cerebrovascular constriction.…”

Section: Vascular Disturbancesmentioning

confidence: 99%

Migraine and motion sickness: What is the link?

Cuomo-Granston

Drummond

2010

Progress in Neurobiology

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The brainstem is a structurally complex region, containing numerous ascending and descending fibres that converge on centres that regulate bodily functions essential to life. Afferent input from the cranial tissues and the special senses is processed, in part, in brainstem nuclei. In addition, brainstem centres modulate the flow of pain messages and other forms of sensory information to higher regions of the brain, and influence the general excitability of these cortical regions. Thus, disruptions in brainstem processing might evoke a complex range of unpleasant symptoms, vegetative changes and neurovascular disturbances and that, together, form attacks of migraine. Migraine is linked with various co-morbid conditions, the most prominent being motion sickness. Symptoms such as nausea, dizziness and headache are common to motion sickness and migraine; moreover, migraine sufferers have a heightened vulnerability to motion sickness. As both maladies involve reflexes that relay in the brainstem, symptoms may share the same neural circuitry. In consequence, subclinical interictal persistence of disturbances in these brainstem pathways could not only increase vulnerability to recurrent attacks of migraine but also increase susceptibility to motion sickness. Mechanisms that mediate symptoms of motion sickness and migraine are explored in this paper. The physiology of motion sickness and migraine is discussed, and neurotransmitters that may be involved in the manifestation of symptoms are reviewed. Recent findings have shed light on the relationship between migraine and motion sickness, and provide insights into the generation of migraine attacks.

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“…Their findings may have in fact been anticipated by Bach et al, who found normal levels of calcitonin gene-related peptide (CGRP) in the cerebrospinal fluid of patients with TTH 12,13 . To date, the most consistent finding in the pathophysiology of CTTH has been the evidence that glyceryl-nitrate (GNT) infusion can induce late-onset tension-type-like headache in CTTH sufferers 14,15 .…”

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confidence: 72%

Neurotrophic factors and tension-type headache: another brick in the wall?

Folchini

Kowacs

2015

Arq. Neuro-Psiquiatr.

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T ension-type headache (TTH) is the most prevalent primary headache and the second most prevalent disorder in the world 1 . However, despite the great progress made in understanding the putative physiological and biological abnormalities of migraines in recent decades 2 , the same cannot be said for their counterpart, TTH, which has been relegated to the background by most investigators 3 and, now neglected 4 , can be considered the "ugly duckling" of headache disorders classified by the International Headache Society (IHS). In what is perhaps a vicious circle, few initiatives have been taken by independent academic or industry-financed researchers to change this situation.The physiological basis of TTH was explored in the 1990s 5, and the findings allowed hypotheses for putative biochemical mechanisms associated with this type of headache to be drawn up 6 . Nevertheless, these hypothetical mechanisms have yet to be confirmed and, with few exceptions, the studies that have been carried out did not use animal models or test these mechanisms to the same level of detail as in migraine studies 2 . It is against this background that the paper in this edition by Domingues et al., who studied the role of neurotrophic factors in TTH down to the molecular level, acquires particular importance 7 . In a well-designed and carefully conducted cross-sectional study, Domingues et al. determined serum levels of brain-derived neurotrophic factor (BDNF), nerve-growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) in forty-eight TTH patients and forty-eight age and gender-matched controls. The authors searched for a correlation between these neurotrophic factors and TTH (both episodic and chronic) as well as other measurable psychosocial variables 7 . Early studies of the pathophysiology of TTH supported the muscle-contraction theory, although TTH can occur with or without pericranial tenderness. The widespread acceptance this theory gained can be observed in a review by Maekawa et al. 8 , who discussed the factors supporting and refuting the putative role of adrenergic receptors and muscle hypoperfusion in myofascial pain.Following a different line of investigation, and probably considering the similarities between migraine and TTH, such as their sharing of common triggers 3,9 , Ashina et al. searched unsuccessfully for changes in neuropeptides such as substance P, neuropeptide Y and vasoactive intestinal polypeptide (VIP) in peripheral blood of patients with chronic tension-type headache (CTTH) 10,11 . Their findings may have in fact been anticipated by Bach et al., who found normal levels of calcitonin gene-related peptide (CGRP) in the cerebrospinal fluid of patients with TTH 12,13 . To date, the most consistent finding in the pathophysiology of CTTH has been the evidence that glyceryl-nitrate (GNT) infusion can induce late-onset tension-type-like headache in CTTH sufferers 14,15 . These findings prompted a cross-over trial, which showed that NG-monomethyl-L-arginine hydrochloride (L-NMMA), an NOS inhib...

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Neurobiology in primary headaches

Cited by 212 publications

References 198 publications

Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

Migraine and motion sickness: What is the link?

Neurotrophic factors and tension-type headache: another brick in the wall?

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