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Current Neuropharmacology 2020The trigeminal nerve is the largest of all cranial nerves. It has three branches that provide the main sensory innervation of the anterior two-thirds of the head and... (Review)
Review
The trigeminal nerve is the largest of all cranial nerves. It has three branches that provide the main sensory innervation of the anterior two-thirds of the head and face. Trigeminal neuralgia (TN) is characterized by sudden, severe, brief, and stabbing recurrent episodes of facial pain in one or more branches of the trigeminal nerve. Pain attacks can occur spontaneously or can be triggered by non-noxious stimuli, such as talking, eating, washing the face, brushing teeth, shaving, a light touch or even a cool breeze. In addition to pain attacks, a proportion of the patients also experience persistent background pain, which along with autonomic signs and prolonged disease duration, represent predictors of worse treatment outcomes. It is now widely accepted that the presence of a neurovascular compression at the trigeminal root entry zone is an anatomic abnormality with a high correlation with classical TN. However, TN may be related to other etiologies, thus presenting different and/or additional features. Since the 1960s, the anticonvulsant carbamazepine is the drug of choice for TN treatment. Although anti-epileptic drugs are commonly used to treat neuropathic pain in general, the efficacy of carbamazepine has been largely limited to TN. Carbamazepine, however, is associated with dose-limiting side-effects, particularly with prolonged usage. Thus, a better understanding and new treatment options are urgently warranted for this rare, but excruciating disease.
Topics: Carbamazepine; Humans; Neuralgia; Trigeminal Nerve; Trigeminal Neuralgia
PubMed: 31608834
DOI: 10.2174/1570159X17666191010094350 -
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 -
Acta Clinica Croatica Sep 2022Trigeminal neuralgia causes severe to excruciating pain that often cannot be successfully reduced with current forms of treatment. The International Association for the... (Review)
Review
Trigeminal neuralgia causes severe to excruciating pain that often cannot be successfully reduced with current forms of treatment. The International Association for the Study of Pain (IASP) defines trigeminal neuralgia as a sudden, usually unilateral, powerful, short, stabbing, recurrent episode of pain in the distribution of one or more branches of the trigeminal nerve. Trigeminal neuralgia can be caused by vascular compression of the trigeminal nerve or a tumor process. Pressure on the nerve itself causes nerve demyelination, which is the cause of abnormal depolarization, resulting in the development of ectopic impulses. Pain can be provoked by brushing teeth, shaving, eating, cold, heat, etc. After diagnosing trigeminal neuralgia, magnetic resonance imaging should be performed to rule out multiple sclerosis, a tumor process that can secondarily cause trigeminal neuralgia. The drug of choice for treating trigeminal neuralgia is still carbamazepine. If pharmacological treatment fails, invasive surgical microvascular decompression, stereotactic radiation therapy (gamma knife), percutaneous balloon micro compression, percutaneous glycerol rhizolysis, and percutaneous radiofrequency (RF) may be used.
Topics: Humans; Trigeminal Neuralgia; Carbamazepine; Trigeminal Nerve; Neuralgia; Neoplasms
PubMed: 36824641
DOI: 10.20471/acc.2022.61.s2.12 -
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 -
Comprehensive Physiology Jan 2015The autonomic nervous system influences numerous ocular functions. It does this by way of parasympathetic innervation from postganglionic fibers that originate from... (Review)
Review
The autonomic nervous system influences numerous ocular functions. It does this by way of parasympathetic innervation from postganglionic fibers that originate from neurons in the ciliary and pterygopalatine ganglia, and by way of sympathetic innervation from postganglionic fibers that originate from neurons in the superior cervical ganglion. Ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction, respectively. Superior cervical ganglion neurons project to the dilator pupillae muscle of the iris to control pupil dilation. Ocular blood flow is controlled both via direct autonomic influences on the vasculature of the optic nerve, choroid, ciliary body, and iris, as well as via indirect influences on retinal blood flow. In mammals, this vasculature is innervated by vasodilatory fibers from the pterygopalatine ganglion, and by vasoconstrictive fibers from the superior cervical ganglion. Intraocular pressure is regulated primarily through the balance of aqueous humor formation and outflow. Autonomic regulation of ciliary body blood vessels and the ciliary epithelium is an important determinant of aqueous humor formation; autonomic regulation of the trabecular meshwork and episcleral blood vessels is an important determinant of aqueous humor outflow. These tissues are all innervated by fibers from the pterygopalatine and superior cervical ganglia. In addition to these classical autonomic pathways, trigeminal sensory fibers exert local, intrinsic influences on many of these regions of the eye, as well as on some neurons within the ciliary and pterygopalatine ganglia.
Topics: Accommodation, Ocular; Animals; Autonomic Nervous System; Eye; Humans; Intraocular Pressure; Neural Pathways; Pupil; Reflex; Regional Blood Flow; Trigeminal Nerve
PubMed: 25589275
DOI: 10.1002/cphy.c140014 -
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 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2016Coronectomy is an alternative to complete removal of an impacted mandibular third molar. Most authors have recommended coronectomy to prevent damage to the inferior... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Coronectomy is an alternative to complete removal of an impacted mandibular third molar. Most authors have recommended coronectomy to prevent damage to the inferior alveolar nerve during surgical extraction of lower third molars. The present study offers a systematic review and metaanalysis of the coronectomy technique.
MATERIAL AND METHODS
A systematic review and meta-analysis was performed based on a PubMed and Cochrane databases search for articles published from 2014 and involving coronectomy of mandibular third molars located near the inferior alveolar nerve canal, with a minimum of 10 cases and a minimum follow-up period of 6 months. After application of the inclusion and exclusion criteria, a total of 12 articles were included in the study.
RESULTS AND DISCUSSION
Coronectomy results in significantly lesser loss of sensitivity of the inferior alveolar nerve and prevents the occurrence of dry socket. No statistically significant differences were observed in the incidence of pain and infection between coronectomy and complete surgical extraction. After coronectomy, the remaining tooth fragment migrates an average of 2 mm within two years.
CONCLUSIONS
Coronectomy is indicated when the mandibular third molar is in contact with the inferior alveolar nerve and complete removal of the tooth may cause nerve damage.
Topics: Humans; Mandible; Mandibular Nerve; Molar, Third; Tooth Crown; Tooth Extraction; Tooth, Impacted; Trigeminal Nerve Injuries
PubMed: 27031064
DOI: 10.4317/medoral.21074 -
Brain Research Bulletin Oct 2018The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited... (Review)
Review
The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism, elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for the patients and high costs for the patients, their family and the society. The reason of low brain penetration of the compounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics. Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce the systemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the anatomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of the nasal route of administration showing its main advantages and limitations of this delivery route for CNS drug targeting.
Topics: Administration, Intranasal; Animals; Blood-Brain Barrier; Brain; Drug Administration Routes; Drug Delivery Systems; Humans; Models, Animal; Nasal Cavity; Trigeminal Nerve
PubMed: 30449731
DOI: 10.1016/j.brainresbull.2018.10.009 -
Indian Journal of Dental Research :... 2018Damage to the inferior alveolar nerve (IAN) while extracting lower third molars is often caused by the intimate relationship between the nerve and the roots of the... (Comparative Study)
Comparative Study
AIM
Damage to the inferior alveolar nerve (IAN) while extracting lower third molars is often caused by the intimate relationship between the nerve and the roots of the teeth. The aim of this study was to compare the sequelae of coronectomy with odontectomy in impacted mandibular third molars.
PATIENTS AND METHODS
This study included thirty patients which were divided into two groups, Group-I (test group) including 15 patients undergoing coronectomy and Group-2 (control group) of 15 patients undergoing odontectomy. Investigations included digital orthopantomogram. The parameters for this study included pain, swelling, nerve paresthesia, trismus, postoperative infection, postoperative wound dehiscence, postoperative pocket depth, and migration.
RESULTS
In Group-1 (coronectomy group), the patients underwent follow-up for 6 months to evaluate migration of the retained mandibular third molar root which was in proximity with the IAN. There was a mean increase in migration when the distance from the inferior border of IAN until the apex of the retained mandibular third molar root was measured which was by 3.43 mm after 6 months of follow up.
CONCLUSION
On statistical analysis, the result in this study showed no statistical difference in both the groups in all the parameters that were taken.
Topics: Adolescent; Adult; Female; Follow-Up Studies; Humans; Male; Mandible; Mandibular Nerve; Molar, Third; Time Factors; Tooth Crown; Tooth Extraction; Tooth Migration; Tooth Root; Tooth, Impacted; Trigeminal Nerve Injuries; Young Adult
PubMed: 30409940
DOI: 10.4103/ijdr.IJDR_549_16