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 genetically-influenced complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea and light and sound sensitivity. Other characterizing symptoms may include vomiting, cognitive dysfunction, allodynia, and dizziness. Exacerbation or worsening of headache symptoms during physical activity is another distinguishing feature.

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

A 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 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.

A medication overuse headache (MOH), also known as a rebound headache, usually occurs when painkillers are taken frequently to relieve headaches. These cases are often referred to as painkiller headaches. Rebound headaches frequently occur daily, can be very painful and are a common cause of chronic daily headache. They typically occur in patients with an underlying headache disorder such as migraine or tension-type headache that "transforms" over time from an episodic condition to chronic daily headache due to excessive intake of acute headache relief medications. MOH is a serious, disabling and well-characterized disorder, which represents a worldwide problem and is now considered the third-most prevalent type of headache. The proportion of patients in the population with Chronic Daily Headache (CDH) who overuse acute medications ranges from 18% to 33%. The prevalence of medication overuse headache (MOH) varies depending on the population studied and diagnostic criteria used. However, it is estimated that MOH affects approximately 1-2% of the general population, but its relative frequency is much higher in secondary and tertiary care.

<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> Medication used for migraines & cluster headaches

Sumatriptan, sold under the brand name Imitrex 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.

<span class="mw-page-title-main">Zolmitriptan</span> Medication used in treatment of migraines

Zolmitriptan, sold under the brand name Zomig among others, is a serotonergic medication which is used in the acute treatment of migraine attacks with or without aura and cluster headaches. It is taken by mouth as a swallowed or disintegrating tablet or as a nasal spray.

The Nociceptive trigeminal inhibition tension suppression system, is a type of occlusal splint that is claimed to prevent headache and migraine by reducing sleep bruxism. Sleep bruxism is purported to lead to a hyperactivity of the trigeminal nerve, often triggering typical migraine events. The hyperactivity of trigeminal neurons during trigemino-nociceptive stimulation is a proposed cause of migraine and is correlated with imaging of migraine sufferers. The objective of the NTI-TSS is to relax the muscles involved in clenching and bruxing, thus supposedly diminishing the chances for migraines and tension headaches to develop through the reduction in nociceptive stimulation normally caused by parafunctional activity. It is sometimes used for temporomandibular joint dysfunction (TMD).

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">Calcitonin gene-related peptide</span> Peptide hormone in animals

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

<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.

<span class="mw-page-title-main">Leptomeningeal cancer</span> Medical condition

Leptomeningeal cancer is a rare complication of cancer in which the disease spreads from the original tumor site to the meninges surrounding the brain and spinal cord. This leads to an inflammatory response, hence the alternative names neoplastic meningitis (NM), malignant meningitis, or carcinomatous meningitis. The term leptomeningeal describes the thin meninges, the arachnoid and the pia mater, between which the cerebrospinal fluid is located. The disorder was originally reported by Eberth in 1870. It is also known as leptomeningeal carcinomatosis, leptomeningeal disease (LMD), leptomeningeal metastasis, meningeal metastasis and meningeal carcinomatosis.

Preventive treatment of migraine can be an important component of migraine management. The goals of preventive therapy are to reduce the frequency, painfulness, and/or duration of migraine attacks, and to increase the effectiveness of abortive therapy. Another reason to pursue prevention is to avoid medication overuse headache (MOH), otherwise known as rebound headache, which can arise from overuse of pain medications, and can result in chronic daily headache. Preventive treatments of migraine include medications, nutritional supplements, lifestyle alterations, and surgery. Prevention is recommended in those who have headaches more than two days a week, cannot tolerate the medications used to treat acute attacks, or those with severe attacks that are not easily controlled.

Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. 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".

Migraine may be treated either prophylactically (preventive) or abortively (rescue) for acute attacks. Migraine is a complex condition; there are various preventive treatments which disrupt different links in the chain of events that occur during a migraine attack. Rescue treatments also target and disrupt different processes occurring during 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">Messoud Ashina</span> Messoud Ashina is a Danish-Azerbaijani neuroscientist

Messoud Ashina is a Danish-Azerbaijani neurologist and neuroscientist. He is currently Professor of Neurology at the University of Copenhagen and Senior Consultant of Neurology at Copenhagen University Hospital - Rigshospitalet. He leads the Human Migraine Research Unit at the Danish Headache Center, Copenhagen University Hospital - Rigshospitalet. Ashina is also Director of the Danish Knowledge Center on Headache Disorders and Past President of the International Headache Society. As of 2024, 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. 19 (2): 115–127. 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. PMC   1917483 . PMID   2158835.
  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. PMC   7164539 . PMID   31160203.
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.