Trigeminovascular system

Last updated

The trigeminovascular system (TVS) refers to neurons and their axonal projections within the trigeminal nerve that project to the cranial meninges and meningeal blood vessels [1] [2] residing on the brain's surface. [3] The term, introduced in 1983 [4] denotes also the neuropeptides contained within axons that are released into the meninges [5] [6] to target vessels and surrounding cells (e.g., mast cells, macrophages, Schwann cells).

Contents

The major drugs used to treat migraine in the 19th and 20th century (ergot alkaloids, triptans) were found by Moskowitz and colleagues [7] [6] to inhibit neuropeptide release from TV axons as their major mechanism of action. Because drugs that block the release of neuropeptides from trigeminovascular fibres are therapeutically relevant for relieving migraine headaches (especially CGRP to date), hence, It has been hypothesized that the trigeminovascular system may be involved in migraine headaches. [3] [8] [9] Studies of the TVS have helped to identify therapeutic targets for migraine including onabotulinum toxin, 5-HT1F receptor agonist (lasmiditan),5-HT1B,D [10] as well as CGRP and its receptor system [11] including both small molecule drugs and biologicals. Numerous experimental studies have established that cortical spreading depolarization, the biological substrate for migraine aura, can discharge trigeminovascular afferents as a cause of head pain and by extension unilateral headache overlying the dysfunctional hemisphere in migraineurs with aura. [12] Hence, the TVS has provided a template for migraine pathophysiology and target for drug discovery.

The history of some discoveries re the TV System are summarised in Ashina, et al. [13]

The Brain Prize for 2021 was awarded to 4 investigators studying the trigeminovascular system and its implications for migraine pathophysiology and treatments.

See also

Related Research Articles

<span class="mw-page-title-main">Migraine</span> Disorder resulting in recurrent moderate-severe headaches

Migraine is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hours to three days. Non-headache symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell. The pain is generally made worse by physical activity during an attack, although regular physical exercise may prevent future attacks. Up to one-third of people affected have aura: typically, it is a short period of visual disturbance that signals that the headache will soon occur. Occasionally, aura can occur with little or no headache following, but not everyone has this symptom.

<span class="mw-page-title-main">Headache</span> Pain in the head or neck

Headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.

<span class="mw-page-title-main">Cluster headache</span> Neurological disorder

Cluster headache (CH) is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s). There is often accompanying eye watering, nasal congestion, or swelling around the eye on the affected side. These symptoms typically last 15 minutes to 3 hours. Attacks often occur in clusters which typically last for weeks or months and occasionally more than a year.

<span class="mw-page-title-main">Pia mater</span> Delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord

Pia mater, often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. Pia mater is medieval Latin meaning "tender mother". The other two meningeal membranes are the dura mater and the arachnoid mater. Both the pia and arachnoid mater are derivatives of the neural crest while the dura is derived from embryonic mesoderm. The pia mater is a thin fibrous tissue that is permeable to water and small solutes. The pia mater allows blood vessels to pass through and nourish the brain. The perivascular space between blood vessels and pia mater is proposed to be part of a pseudolymphatic system for the brain. When the pia mater becomes irritated and inflamed the result is meningitis.

<span class="mw-page-title-main">Sumatriptan</span> 5-HT receptor agonist medication used for migraines & cluster headaches

Sumatriptan, sold commonly under brand names Imitrex and Treximet among others, is a medication used to treat migraine headaches and cluster headaches. It is taken orally, intranasally, or by subcutaneous injection. Therapeutic effects generally occur within three hours.

<span class="mw-page-title-main">Triptan</span> Class of pharmaceutical drugs

Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, they do not provide preventive treatment and are not considered a cure. They are not effective for the treatment of tension–type headache, except in persons who also experience migraines. Triptans do not relieve other kinds of pain.

Neurogenic inflammation is inflammation arising from the local release by afferent neurons of inflammatory mediators such as Substance P, Calcitonin Gene-Related Peptide (CGRP), neurokinin A (NKA), and endothelin-3 (ET-3). In such neurons, release of these pro-inflammatory mediators is thought to be triggered by the activation of ion channels that are the principal detectors of noxious environmental stimuli. In particular, the heat/capsaicin receptor TRPV1 and the irritant/wasabi receptor TRPA1. TRPA1 channels stimulated by lipopolysaccharide (LPS) may also cause acute neurogenic inflammation. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and calcitonin gene-related peptide; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established.

<span class="mw-page-title-main">Anterior ethmoidal nerve</span> Nerve of the nose

The anterior ethmoidal nerve is a nerve of the nose. It is a branch of the nasociliary nerve, itself a branch of the ophthalmic nerve (V1). It provides sensory innervation to some structures around the nasal cavity.

Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 (intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produced by thyroid C cells whilst CGRP is secreted and stored in the nervous system. This peptide, in humans, exists in two forms: CGRP alpha, and CGRP beta. α-CGRP is a 37-amino acid neuropeptide and is formed by alternative splicing of the calcitonin/CGRP gene located on chromosome 11. β-CGRP is less studied. In humans, β-CGRP differs from α-CGRP by three amino acids and is encoded in a separate, nearby gene. The CGRP family includes calcitonin (CT), adrenomedullin (AM), and amylin (AMY).

<span class="mw-page-title-main">Antimigraine drug</span> Medication intended to reduce the effects or intensity of migraine headache

Antimigraine drugs are medications intended to reduce the effects or intensity of migraine headache. They include drugs for the treatment of acute migraine symptoms as well as drugs for the prevention of migraine attacks.

Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. It is applied three times daily for a maximum of three months. Zucapsaicin is a member of phenols and a member of methoxybenzenes It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1 that reduces pain, and improves articular functions. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use.

<span class="mw-page-title-main">Umbellulone</span> Chemical compound

Umbellulone is a headache-inducing monoterpene ketone found in the leaves of the tree Umbellularia californica, sometimes known as the "headache tree".

Calcitonin gene-related peptide (CGRP) receptor antagonists are a class of drugs that act as antagonists of the calcitonin gene-related peptide receptor (CGRPR).

Migraine treatment may be either prophylactic (preventive) or abortive (rescue). Prevention is better than cure, so the ideal treatment goal is to prevent migraine attacks. Because migraine is an exceedingly complex condition, there are various preventive treatments which have their effect by disrupting different links in the chain of events that occur during a migraine attack. As rescue treatments also target and disrupt different processes occurring during migraine, these are summarized, with their relative merits and demerits.

The parabrachial nuclei, also known as the parabrachial complex, are a group of nuclei in the dorsolateral pons that surrounds the superior cerebellar peduncle as it enters the brainstem from the cerebellum. They are named from the Latin term for the superior cerebellar peduncle, the brachium conjunctivum. In the human brain, the expansion of the superior cerebellar peduncle expands the parabrachial nuclei, which form a thin strip of grey matter over most of the peduncle. The parabrachial nuclei are typically divided along the lines suggested by Baxter and Olszewski in humans, into a medial parabrachial nucleus and lateral parabrachial nucleus. These have in turn been subdivided into a dozen subnuclei: the superior, dorsal, ventral, internal, external and extreme lateral subnuclei; the lateral crescent and subparabrachial nucleus along the ventrolateral margin of the lateral parabrachial complex; and the medial and external medial subnuclei

<span class="mw-page-title-main">CP-122,288</span> Chemical compound

CP-122,288 is a drug which acts as a potent and selective agonist for the 5-HT1B, 5-HT1D and 5-HT1F serotonin receptor subtypes. It is a derivative of the migraine medication sumatriptan, but while CP-122,288 is 40,000 times more potent than sumatriptan as an inhibitor of neurogenic inflammation and plasma protein extravasation, it is only twice as potent as a constrictor of blood vessels. In human trials, CP-122,288 was not found to be effective as a treatment for migraine, but its selectivity for neurogenic anti-inflammatory action over vasoconstriction has made it useful for research into the underlying causes of migraine.

Eptinezumab, sold under the brand name Vyepti, is a medication used for the preventive treatment of migraine in adults. It is a monoclonal antibody that targets calcitonin gene-related peptides (CGRP) alpha and beta. It is administered by intravenous infusion.

<span class="mw-page-title-main">Rimegepant</span> Medication for acute migraine in adults

Rimegepant, sold under the brand name Nurtec ODT among others, is a medication used for the acute treatment of migraine with or without aura in adults and the preventative treatment of episodic migraine in adults. It is taken by mouth to dissolve on or under the tongue. It works by blocking CGRP receptors.

<span class="mw-page-title-main">Messoud Ashina</span> Messoud Ashina is a Danish-Azerbaijani neuroscientist

Messoud Ashina is a Danish-Azerbaijani neurologist and neuroscientist. He is currently a Professor of Neurology at the University of Copenhagen and leads the Human Migraine Research Unit at the Danish Headache Center, Rigshospitalet. Ashina is also the Director of the Danish Knowledge Center on Headache Disorders and the past President of the International Headache Society. As of 2023, Ashina is ranked as the world's leading expert on headache disorders by Expertscape.

<span class="mw-page-title-main">Recurrent painful ophthalmoplegic neuropathy</span> Medical condition

Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine (OM), is a rare neurological disorder that is characterized by repeated headache attacks and reversible ipsilateral paresis of one or more ocular cranial nerves (CN). Oculomotor nerve (CNIII) is by far the most common cranial nerve involves in RPON, while abducens nerve (CNVI) and trochlear nerve (CNIV) involvements are also reported. Globally, RPON was estimated to have an annual incidence rate of 0.7 per million as of 1990, no further epidemiological studies have been conducted. It occurs more often in children and females.

References

  1. ↑ Moskowitz, MichaelA.; Romero, Jorge; Reinhard, JohnF.; Melamed, Eldad; Pettibone, DouglasJ. (October 1979). "NEUROTRANSMITTERS AND THE FIFTH CRANIAL NERVE: IS THERE A RELATION TO THE HEADACHE PHASE OF MIGRAINE?". The Lancet. 314 (8148): 883–885. doi:10.1016/s0140-6736(79)92692-8. ISSN   0140-6736.
  2. ↑ Moskowitz, Michael A. (August 1984). "The neurobiology of vascular head pain". Annals of Neurology. 16 (2): 157–168. doi:10.1002/ana.410160202. ISSN   0364-5134.
  3. 1 2 May, A.; Goadsby, P. J. (1999). "The Trigeminovascular System in Humans: Pathophysiologic Implications for Primary Headache Syndromes of the Neural Influences on the Cerebral Circulation". Journal of Cerebral Blood Flow & Metabolism: 115. doi: 10.1097/00004647-199902000-00001 .
  4. ↑ Liu-Chen, Lee-Yuan; Mayberg, Marc R.; Moskowitz, Michael A. (May 1983). "Immunohistochemical evidence for a substance P-containing trigeminovascular pathway to pial arteries in cats". Brain Research. 268 (1): 162–166. doi:10.1016/0006-8993(83)90402-x. ISSN   0006-8993.
  5. ↑ Moskowitz, M.A.; Brody, M.; Liu-Chen, L.-Y. (August 1983). "In vitro release of immunoreactive substance P from putative afferent nerve endings in bovine pia arachnoid". Neuroscience. 9 (4): 809–814. doi:10.1016/0306-4522(83)90269-5. ISSN   0306-4522.
  6. 1 2 Buzzi, M (November 1991). "Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion". Neuropharmacology. 30 (11): 1193–1200. doi:10.1016/0028-3908(91)90165-8. ISSN   0028-3908.
  7. ↑ Buzzi, M. Gabriella; Moskowitz, Midiael A. (January 1990). "The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater". British Journal of Pharmacology. 99 (1): 202–206. doi:10.1111/j.1476-5381.1990.tb14679.x. ISSN   0007-1188.
  8. ↑ Fanciullacci, M.; Alessandri, M.; Sicuteri, R.; Marabini, S. (1997). "Responsiveness of the trigeminovascular system to nitroglycerine in cluster headache patients". Brain. 120 (2): 283. doi: 10.1093/brain/120.2.283 .
  9. ↑ Noseda, R.; Jakubowski, M.; Kainz, V.; Borsook, D.; Burstein, R. (2011). "Cortical Projections of Functionally Identified Thalamic Trigeminovascular Neurons: Implications for Migraine Headache and Its Associated Symptoms". Journal of Neuroscience. 31 (40): 14204–14217. doi:10.1523/JNEUROSCI.3285-11.2011. PMC   3501387 . PMID   21976505.
  10. ↑ Moskowitz, MA; et al. (November 2022). "Migraine research comes of age in the 21st century". Lancet Neurology. 21 (11): 955–958. doi:10.1016/S1474-4422(22)00398-2.
  11. ↑ Warfvinge, Karin; Edvinsson, Lars (2013-05-13). "Pearls and pitfalls in neural CGRP immunohistochemistry". Cephalalgia. 33 (8): 593–603. doi:10.1177/0333102412472072. ISSN   0333-1024.
  12. ↑ Bolay, Hayrunnisa; Reuter, Uwe; Dunn, Andrew K.; Huang, Zhihong; Boas, David A.; Moskowitz, Michael A. (February 2002). "Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model". Nature Medicine. 8 (2): 136–142. doi:10.1038/nm0202-136. ISSN   1078-8956.
  13. ↑ Ashina, Messoud; Hansen, Jakob Møller; Do, Thien Phu; Melo-Carrillo, Agustin; Burstein, Rami; Moskowitz, Michael A (August 2019). "Migraine and the trigeminovascular system—40 years and counting". Lancet Neurology. 18 (8): 795–804. doi:10.1016/s1474-4422(19)30185-1. ISSN   1474-4422.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.