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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 Journal of Headache and Pain Nov 2022Excruciating trigeminal neuralgia (TN) management is very difficult and severely affects the patient's quality of life. Earlier studies have shown that the trigeminal... (Review)
Review
Excruciating trigeminal neuralgia (TN) management is very difficult and severely affects the patient's quality of life. Earlier studies have shown that the trigeminal ganglion (TG) comprises several receptors and signal molecules that are involved in the process of peripheral sensitization, which influences the development and persistence of neuropathic pain. Targeting TG can modulate this sensitization pathway and mediate the pain-relieving effect. So far,there are few studies in which modulation approaches to TG itself have been suggested so far. "Trigeminal ganglion modulation" and "trigeminal neuralgia" were used as search phrases in the Scopus Index and PubMed databases to discover articles that were pertinent to the topic. In this review, we address the role of the trigeminal ganglion in TN and underlying molecules and neuropeptides implicated in trigeminal pain pathways in processing pathological orofacial pain. We also reviewed different modulation approaches in TG for TN management. Furthermore, we discuss the prospect of targeting trigeminal ganglion to manage such intractable pain.
Topics: Humans; Trigeminal Ganglion; Quality of Life; Trigeminal Neuralgia; Neuralgia; Facial Pain
PubMed: 36424545
DOI: 10.1186/s10194-022-01512-x -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2022The article summarizes data about the structural and functional organization of the sensory ganglion of V cranial nerve - trigeminal, or Gassesrian, ganglion....
The article summarizes data about the structural and functional organization of the sensory ganglion of V cranial nerve - trigeminal, or Gassesrian, ganglion. Information about its discovery, embryonic development, anatomy and topography, features of cyto- and histoarchitectonics are given, the role of neurotransmitters of trigeminal ganglion neurons in nociception mechanisms is reflected, the functional significance of the trigeminal system and clinical aspects of the lesion of the Gasserian ganglion are described.
Topics: Humans; Trigeminal Ganglion; Trigeminal Neuralgia
PubMed: 36537645
DOI: 10.17116/jnevro2022122121143 -
The New England Journal of Medicine Nov 2020
Review
Topics: Adolescent; Adult; Algorithms; Anti-Inflammatory Agents, Non-Steroidal; Child; Drug Therapy, Combination; Humans; Migraine Disorders; Trigeminal Ganglion; Tryptamines
PubMed: 33211930
DOI: 10.1056/NEJMra1915327 -
The Journal of Physiological Sciences :... Sep 2016Peripheral tissue inflammation can alter the properties of somatic sensory pathways, causing behavioral hypersensitivity and resulting in increased responses to pain... (Review)
Review
Peripheral tissue inflammation can alter the properties of somatic sensory pathways, causing behavioral hypersensitivity and resulting in increased responses to pain caused by noxious stimulation (hyperalgesia) and normally innocuous stimulation (allodynia). These hypersensitivities for nociception are caused by changes in the excitability of trigeminal ganglion (TG) neurons. These changes alter sensory information processing in the neurons in the medullary trigeminal nucleus of caudalis. Increasing information is becoming available regarding trigeminal neuron-neuron/neuron-satellite glial cells (SGCs) communication. The activation of intraganglionic communication plays an important role in the creation and maintenance of trigeminal pathological pain. Therefore, in this review, we focus on the recent findings for sensory functions and pharmacological modulation of TG neurons and SGCs under normal and pathological conditions, and we discuss potential therapeutic targets in glia-neuronal interactions for the prevention of trigeminal neuropathic and inflammatory pain.
Topics: Animals; Hyperalgesia; Neurons; Nociception; Pain; Trigeminal Ganglion
PubMed: 27023716
DOI: 10.1007/s12576-016-0448-1 -
World Neurosurgery Apr 2021The anatomy and spatial relationships of the dural sac comprising the Meckel cave (MC) and its ensheathed trigeminal ganglion (TG) are exceedingly intricate and complex....
BACKGROUND
The anatomy and spatial relationships of the dural sac comprising the Meckel cave (MC) and its ensheathed trigeminal ganglion (TG) are exceedingly intricate and complex. There are conflicting accounts in the literature regarding the dural configuration of the MC around the ganglion and the dual embryology of the MC and TG is still unclear.
METHODS
A combined systematic and narrative literature review was conducted to collate articles addressing MC and TG anatomy, in addition to their embryology, role in tumor spread, somatotopy, and association with trigeminal neuralgia.
RESULTS
Three key anatomic models by Paturet (1964), Lazorthes (1973), and Lang and Ferner (1983) have been put forward to show the arrangement of the MC around the TG. The TG is formed from both neural crest and placodal cells and drags the enveloping dura caudally to form the MC prolongation during development. Both a mediolateral and dorsoventral somatotopic arrangement of neurons exists in the TG, which corresponds to the 3 nerve divisions, of which V2 and V3 are prone to perineural tumor spread along their course.
CONCLUSIONS
Sound knowledge concerning the dural arrangement of the MC and the trigeminal divisions will be invaluable in optimally treating cancers in this region, and understanding TG somatotopy will immensely improve treatment of trigeminal neuralgia in terms of specificity, efficacy, and positive patient outcomes.
Topics: Cranial Fossa, Posterior; Dura Mater; Humans; Neurosurgical Procedures; Trigeminal Ganglion; Trigeminal Neuralgia
PubMed: 33516868
DOI: 10.1016/j.wneu.2021.01.081 -
Current Protocols in Cell Biology Jun 2019Visualization of dynamic cellular activity has greatly expanded our understanding of brain function. Recently, there has been an increasing number of studies imaging...
Visualization of dynamic cellular activity has greatly expanded our understanding of brain function. Recently, there has been an increasing number of studies imaging rodent brain activity in real time. However, traditional in vivo calcium imaging technology has been limited to superficial brain structures. Because the trigeminal ganglion (TG) is located deep within the cranial cavity of mice, few studies have been able to access to it. To circumvent this limitation, overlying brain tissue must be removed to expose the TG so that optical recording can access deep brain neural ensembles. This unit describes a procedure for conducting non-survival surgery to visualize the TG in live mice. Obtaining large ensembles of direct, real-time readouts of sensory neuron signaling, providing temporal and spatial information across the TG, will help to define the cellular basis of orofacial somatic sensing and pain perception. © 2019 by John Wiley & Sons, Inc.
Topics: Animals; Brain Mapping; Mice; Neurosurgical Procedures; Pain Perception; Trigeminal Ganglion
PubMed: 30724481
DOI: 10.1002/cpcb.84 -
Pain Feb 1994Idiosyncrasies of trigeminal neuralgia provide both clues and constraints on candidate hypotheses concerning the underlying neural mechanism. After reviewing the key... (Review)
Review
Idiosyncrasies of trigeminal neuralgia provide both clues and constraints on candidate hypotheses concerning the underlying neural mechanism. After reviewing the key clinical aspects of the disease, we propose here a novel hypothesis based on recent findings from experimental nerve-injury preparations. The hypothesis states that trigger stimuli set off bursts of activity in a small cluster of trigeminal ganglion (TRG) neurons that have been rendered hyperexcitable as a result of TRG or trigeminal root damage. Activity then spreads from this "TRG ignition focus" to encompass more widespread portions of the ganglion. After a brief period of autonomous firing (seconds to minutes), activity is quenched and a refractory period is initiated by an intrinsic suppressive (hyperpolarizing) process engaged as a result of the rapid firing. The primary abnormality resides in the TRG and trigeminal root, rather than in the skin or the CNS. Because of this, sensation is essentially normal between periods of ectopic paroxysmal TRG discharge.
Topics: Electrophysiology; Humans; Trigeminal Ganglion; Trigeminal Neuralgia
PubMed: 8008402
DOI: 10.1016/0304-3959(94)90086-8 -
Microscopy Research and Technique Jun 2013The morphology of the trigeminal ganglion in human fetus was investigated by means of the tract-tracing method using the lipophilic dye DiI-C18-(3) (1,1'-double...
The morphology of the trigeminal ganglion in human fetus was investigated by means of the tract-tracing method using the lipophilic dye DiI-C18-(3) (1,1'-double octadecane 3,3,3'3'-tetramethyl indole carbonyl cyanine-perchlorate), hematoxylin-eosin (HE) stain, and three-dimensional computer reconstruction models. The trigeminal ganglion was flat in the dorsoventral direction, and DiI staining revealed that the trigeminal ganglion cells were somatotopically distributed in the ganglion in a way that reflected the mediolateral order of the three branches. Ganglion cells of the ophthalmic nerve were distributed in the anteromedial part of the trigeminal ganglion, those of the mandibular nerve were in the posterolateral part, and those of the maxillary nerve were localized in the intermediate part. DiI labeled both ganglion cells and nerve fibers in the trigeminal ganglion; the ganglion cells varied in size and appeared as round- or oval-shaped, the neurites connected the cell soma, and some bipolar neurons were also observed. The number of embryonic trigeminal ganglion cells did not significantly change with gestational age, but the cell diameter, area, and perimeter significantly increased. The motor root leaves the pons, runs along the sensory root, passes the ventral surface of the ganglion, and finally runs together with the mandibular nerve. The findings reported here elucidate the morphology, development, and somatotopic organization of the trigeminal ganglion and reveal the trigeminal nerve motor root pathway along the trigeminal ganglion and mandibular nerve in the human fetus.
Topics: Fetus; Humans; Imaging, Three-Dimensional; Microscopy; Neuroanatomical Tract-Tracing Techniques; Staining and Labeling; Trigeminal Ganglion
PubMed: 23495217
DOI: 10.1002/jemt.22204 -
Asian Journal of Surgery Jun 2023
Topics: Humans; Trigeminal Ganglion; Gestures; Teaching; Anatomy
PubMed: 36513553
DOI: 10.1016/j.asjsur.2022.11.137