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Headache May 2019The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene-related peptide (CGRP) within... (Review)
Review
OBJECTIVE
The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene-related peptide (CGRP) within the context of the trigeminovascular system.
BACKGROUND
Migraine is a prevalent and disabling neurological disease that is characterized in part by intense, throbbing, and unilateral headaches. Despite recent advances in understanding its pathophysiology, migraine still represents an unmet medical need, as it is often underrecognized and undertreated. Although CGRP has been known to play a pivotal role in migraine for the last 2 decades, this has now received more interest spurred by the early clinical successes of drugs that block CGRP signaling in the trigeminovascular system.
DESIGN
This narrative review presents an update on the role of CGRP within the trigeminovascular system. PubMed searches were used to find recent (ie, 2016 to November 2018) published articles presenting new study results. Review articles are also included not as primary references but to bring these to the attention of the reader. Original research is referenced in describing the core of the narrative, and review articles are used to support ancillary points.
RESULTS
The trigeminal ganglion neurons provide the connection between the periphery, stemming from the interface between the primary afferent fibers of the trigeminal ganglion and the meningeal vasculature and the central terminals in the trigeminal nucleus caudalis. The neuropeptide CGRP is abundant in trigeminal ganglion neurons, and is released from the peripheral nerve and central nerve terminals as well as being secreted within the trigeminal ganglion. Release of CGRP from the peripheral terminals initiates a cascade of events that include increased synthesis of nitric oxide and sensitization of the trigeminal nerves. Secreted CGRP in the trigeminal ganglion interacts with adjacent neurons and satellite glial cells to perpetuate peripheral sensitization, and can drive central sensitization of the second-order neurons. A shift in central sensitization from activity-dependent to activity-independent central sensitization may indicate a mechanism driving the progression of episodic migraine to chronic migraine. The pathophysiology of cluster headache is much more obscure than that of migraine, but emerging evidence suggests that it may also involve hypersensitivity of the trigeminovascular system. Ongoing clinical studies with therapies targeted at CGRP will provide additional, valuable insights into the pathophysiology of this disorder.
CONCLUSIONS
CGRP plays an essential role in the pathophysiology of migraine. Treatments that interfere with the functioning of CGRP in the peripheral trigeminal system are effective against migraine. Blocking sensitization of the trigeminal nerve by attenuating CGRP activity in the periphery may be sufficient to block a migraine attack. Additionally, the potential exists that this therapeutic strategy may also alleviate cluster headache as well.
Topics: Animals; Calcitonin Gene-Related Peptide; Humans; Migraine Disorders; Neuroglia; Neurons; Nociception; Trigeminal Ganglion; Trigeminal Nerve
PubMed: 30982963
DOI: 10.1111/head.13529 -
The Lancet. Neurology Aug 2019The underlying causes of migraine headache remained enigmatic for most of the 20th century. In 1979, The Lancet published a novel hypothesis proposing an integral role... (Review)
Review
The underlying causes of migraine headache remained enigmatic for most of the 20th century. In 1979, The Lancet published a novel hypothesis proposing an integral role for the neuropeptide-containing trigeminal nerve. This hypothesis led to a transformation in the migraine field and understanding of key concepts surrounding migraine, including the role of neuropeptides and their release from meningeal trigeminal nerve endings in the mechanism of migraine, blockade of neuropeptide release by anti-migraine drugs, and activation and sensitisation of trigeminal afferents by meningeal inflammatory stimuli and upstream role of intense brain activity. The study of neuropeptides provided the first evidence that antisera directed against calcitonin gene-related peptide (CGRP) and substance P could neutralise their actions. Successful therapeutic strategies using humanised monoclonal antibodies directed against CGRP and its receptor followed from these findings. Nowadays, 40 years after the initial proposal, the trigeminovascular system is widely accepted as having a fundamental role in this highly complex neurological disorder and provides a road map for future migraine therapies.
Topics: Cardiovascular System; Humans; Migraine Disorders; Neural Pathways; Trigeminal Nerve
PubMed: 31160203
DOI: 10.1016/S1474-4422(19)30185-1 -
International Journal of Molecular... Mar 2022Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying... (Review)
Review
Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.
Topics: Animals; Facial Pain; Humans; Multiple Sclerosis; Neuralgia; Trigeminal Nerve; Trigeminal Neuralgia
PubMed: 35408959
DOI: 10.3390/ijms23073604 -
Handbook of Clinical Neurology 2019The trigeminal sensory nerve fiber branches supply afferent information from the skin and mucous membranes of the face and head and the oral cavity regarding information... (Review)
Review
The trigeminal sensory nerve fiber branches supply afferent information from the skin and mucous membranes of the face and head and the oral cavity regarding information on temperature, touch, and pain. Under normal conditions, the trigeminal nerve serves to provide important information from nerve fibers and tissues using specialized receptors sensitive for irritant and painful stimuli. The current scientific consensus indicates that nerve endings responsible for chemical and thermal sensitivity of the skin and mucous membranes are the same nerves responsible for nociception. This "chemesthetic sense" allows many vertebrates to detect chemical agonists that induce sensations such as touch, burning, stinging, tingling, or changes in temperature. Research has been under way for many years to determine how exposure of the oral and/or nasal cavity to compounds that elicit pungent or irritant sensations can produce these sensations. In addition, these chemicals can alter other sensory information such as taste and smell to affect the flavor of foods and beverages. We now know that these 'chemesthetic molecules' are agonists of molecular receptors, which exist on primary afferent nerve fibers that innervate the orofacial area. However, under pathophysiologic conditions, over- or underexpression or activity of these receptors may lead to painful orotrigeminal syndromes. Some of these individual receptors are discussed in detail, including transient receptor potential channels and acid sensing ion channels, among others.
Topics: Animals; Humans; Mouth; Nerve Fibers; Pain; Skin; Taste; Trigeminal Nerve
PubMed: 31604548
DOI: 10.1016/B978-0-444-63855-7.00013-7 -
European Review For Medical and... Sep 2018This review aims to describe trigeminal neuralgia and the molecular basis contributing to the pathophysiology of this condition by focusing on the state of the art. (Review)
Review
OBJECTIVE
This review aims to describe trigeminal neuralgia and the molecular basis contributing to the pathophysiology of this condition by focusing on the state of the art.
PATIENTS AND METHODS
An electronic search of PubMed was performed using the following keywords: "trigeminal neuralgia" AND "classification", "pathophysiology," "molecular basis" and "mitochondrial role."
RESULTS
Mitochondrial abnormality, whether functional or morphological, can contribute to neurological disorders. Additionally, one recent finding showed that gain-of-function mutation in the voltage-gated sodium channel NaV1.6 contributes to the pathophysiology of trigeminal neuralgia by increasing the excitability of trigeminal nerve ganglion neurons. It also exacerbates the pathophysiology of vascular compression. Healing of the trigeminal nerve is controlled by many molecular signaling pathways, including extracellular-signal-regulated kinase, c-Jun, p38, Notch, and mitogen-activated protein kinases.
CONCLUSIONS
More investigations regarding the gain-of-function mutation of NaV1.6 sodium channels are essential for the diagnosis and treatment of trigeminal nerve disorders, regardless of whether these are associated with vascular compression or not.
Topics: Gain of Function Mutation; Genetic Predisposition to Disease; Humans; NAV1.6 Voltage-Gated Sodium Channel; Phenotype; Prognosis; Risk Factors; Signal Transduction; Trigeminal Nerve; Trigeminal Nerve Diseases
PubMed: 30229854
DOI: 10.26355/eurrev_201809_15844 -
Acta Medica Academica Aug 2021Trigeminal neuralgia is a long-term facial pain syndrome. Our aim was to review the anatomy of the trigeminal nerve and its anatomical relationship with the adjacent... (Review)
Review
OBJECTIVE
Trigeminal neuralgia is a long-term facial pain syndrome. Our aim was to review the anatomy of the trigeminal nerve and its anatomical relationship with the adjacent structures that may contribute to the pathogenesis of trigeminal neuralgia METHODS: Eligible articles were identified by a search of the Medline Embase, Pubmed Cinahl and Google Scholar bibliographical databases. We checked all the references of the relevant reviews and eligible articles that our search retrieved, in order to identify potentially eligible conference abstracts. Titles of interest were further reviewed by abstract. Case reports were excluded.
RESULTS
Trigeminal neuralgia syndrome seems to be caused by anatomical variations of the trigeminal nerve and its adjacent anatomical structures, mainly through compression. We depict the causes, the pathogenesis, and the clinical manifestations of the syndrome. The classification, diagnostic approach, differential diagnosis, and treatment modalities are also presented and they may be personalized according to the anatomical variations of the trigeminal nerve present, which may lead to trigeminal neuralgia syndrome.
CONCLUSION
It is very important to be very careful in cases of new emerging neuralgia and to avoid the term "idiopathic" until proven otherwise by validating the newer and more appropriate tests and diagnostic criteria. Current data are insufficient and future research is needed in order to discover innovative and more effective treatments of trigeminal neuralgia, considering the anatomy and the anatomical variations of the trigeminal nerve.
Topics: Humans; Treatment Outcome; Trigeminal Nerve; Trigeminal Neuralgia
PubMed: 34847681
DOI: 10.5644/ama2006-124.344 -
Acta Clinica Croatica Jun 2019The whole human body receives rich sensory innervation with only one exception and that is the brain tissue. The orofacial region is hence no exception. The head region... (Review)
Review
The whole human body receives rich sensory innervation with only one exception and that is the brain tissue. The orofacial region is hence no exception. The head region consequently receives a rich network of sensory nerves making it special because the two types of sensory fibres, visceral and somatic overlap, especially in the pharynx. Also, different pain syndromes that affect this region are rather specific in comparison to their presentation in other body regions. With this review article we wanted to show the detailed anatomy of the peripheral sensory pathways, because of its importance in everyday body functions (eating, drinking, speech) as well as the importance it has in pathological conditions (pain syndromes), in diagnostics and regional analgesia and anaesthesia.
Topics: Afferent Pathways; Face; Glossopharyngeal Nerve; Humans; Muscle, Skeletal; Pain; Pharynx; Trigeminal Nerve; Vagus Nerve
PubMed: 31741557
DOI: 10.20471/acc.2019.58.s1.05 -
Chemical Senses May 2019Mouthfeel refers to the physical or textural sensations in the mouth caused by foods and beverages that are essential to the acceptability of many edible products. The... (Review)
Review
Mouthfeel refers to the physical or textural sensations in the mouth caused by foods and beverages that are essential to the acceptability of many edible products. The sensory subqualities contributing to mouthfeel are often chemogenic in nature and include heat, burning, cooling, tingling, and numbing. These "chemesthetic" sensations are a result of the chemical activation of receptors that are associated with nerve fibers mediating pain and mechanotransduction. Each of these chemesthetic sensations in the oral cavity are transduced in the nervous system by a combination of different molecular channels/receptors expressed on trigeminal nerve fibers that innervate the mouth and tongue. The molecular profile of these channels and receptors involved in mouthfeel include many transient receptor potential channels, proton-sensitive ion channels, and potassium channels to name a few. During the last several years, studies using molecular and physiological approaches have significantly expanded and enhanced our understanding of the neurobiological basis for these chemesthetic sensations. The purpose of the current review is to integrate older and newer studies to present a comprehensive picture of the channels and receptors involved in mouthfeel. We highlight that there still continue to be important gaps in our overall knowledge on flavor integration and perception involving chemesthetic sensations, and these gaps will continue to drive future research direction and future investigation.
Topics: Humans; Mouth; Receptors, Odorant; Sensation; Taste; Trigeminal Nerve
PubMed: 31039245
DOI: 10.1093/chemse/bjz016 -
Cell Oct 2020Ophthalmic, maxillary, and mandibular branches of the trigeminal nerve provide sensory innervation to orofacial tissues. Trigeminal sensory neurons respond to a diverse...
Ophthalmic, maxillary, and mandibular branches of the trigeminal nerve provide sensory innervation to orofacial tissues. Trigeminal sensory neurons respond to a diverse array of sensory stimuli to generate distinct sensations, including thermosensation, mechanosensation, itching, and pain. These sensory neurons also detect the distinct sharpness or pungency of many foods and beverages. This SnapShot highlights the transduction ion channels critical to orofacial sensation.
Topics: Cranial Nerves; Humans; Neurons, Afferent; Pain; Sensation; Trigeminal Nerve
PubMed: 33007264
DOI: 10.1016/j.cell.2020.08.014 -
BMC Neurology Oct 2022Neurovascular compression (NVC) produces morphological changes on the trigeminal nerve root is considered the cause of trigeminal neuralgia (TN), but there were some...
OBJECTIVES
Neurovascular compression (NVC) produces morphological changes on the trigeminal nerve root is considered the cause of trigeminal neuralgia (TN), but there were some patients with TN found no NVC, and also NVC was found in asymptomatic individuals. Many studies found tight relationships of TN and morphological structures of trigeminal nerve. We designed this study to explore the correlation between multiplanar reconstruction (MPR) trigeminal nerve angulation (TNA) and TN.
METHODS
Patients with classical symptoms of TN were recruited as observation group (OG) in this study, 50 healthy controls were enrolled as control group (CG), the OG was further subtyped into young patients (YP), middle-aged patients (MP) and old patients (OP) based to the onset age of symptoms, and also divided into patients with or without trigger maneuvers (TM) based on the presence of TM or not. All the participants underwent magnetic resonance (MR) examinations in same device, bilateral TNA measurements were carried out in OG and CG, then TNA was compared between different groups or subgroups. All images were interpreted by two radiologists who were blinded to the study, diagnosis of TN was made by two senior neurosurgery professors.
RESULT
Ultimately, 95 patients with primary TN were recruited in OG, aged from 25 to 84 (61.15 ± 12.70) years with a course of 0.5 to 30 (5.03 ± 5.41) years, their onset age ranged from 24 to 82 (56.13 ± 11.98) years. There were 34 males and 61 females in OG, and 58 cases involved right side. The CG aged from 22 to 85 (61.86 ± 13.03) years. No statistical difference was found between the age of OG and CG(p = 0.76), and also the bilateral TNA of CG (154.92 ± 16.90° vs 155.55 ± 17.03°, p > 0.05), while TNA of OG was significantly smaller than CG (150.78 ± 11.29° vs 155.24 ± 16.88°, p = 0.019). In OG, TNA on the affected side was significantly smaller than the unaffected side (149.29 ± 12.44° vs 152.27 ± 9.85°, p = 0.014). TNA showed a positive correlation with onset age of patients with TN, as TNA on the affected side of YP was significantly smaller than MP and OP (139.00 ± 11.64° vs 148.86 ± 11.54°, 139.00 ± 11.64° vs 152.18 ± 12.61°, p = 0.004 and 0.026). Furthermore, patients with TM showed smaller TNA than those without TM (147.05 ± 11.30° vs 164.75 ± 8.39°, p < 0.001).
CONCLUSIONS
This study suggested that TNA might play a role in TN, small TNA could be a risk factor of TN. Furthermore, patients with small TNA are more likely to combine with TM, but more studies are needed to explore the exact role of TNA in TN.
Topics: Adult; Aged; Aged, 80 and over; Correlation of Data; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Trigeminal Nerve; Trigeminal Neuralgia; Young Adult
PubMed: 36224533
DOI: 10.1186/s12883-022-02906-9