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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 -
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 -
Current Opinion in Ophthalmology Nov 2019To review ocular manifestations and complications of herpes simplex virus (HSV) and discuss recent advancements in diagnostic and treatment strategy. (Review)
Review
PURPOSE OF REVIEW
To review ocular manifestations and complications of herpes simplex virus (HSV) and discuss recent advancements in diagnostic and treatment strategy.
RECENT FINDINGS
In-vivo confocal microscopy has expanded our understanding of corneal nerve degeneration, corneal dendritic cell activity, and changes in biomechanical properties in HSV keratitis. Although currently available only as a research tool, metagenomic deep sequencing has the potential to improve diagnostic accuracy beyond the well established PCR technology, especially in atypical cases. Development of an HSV vaccine has shown some encouraging results in a murine model. New treatment options for neurotrophic cornea offer promise, specifically cenegermin nerve growth factor.
SUMMARY
Ocular herpes simplex infection and its complications continue to cause significant visual burden and decreased quality of life. Familiarity with its clinical features, wider adoption of viral PCR diagnostic technology, and recognition of the need for long-term maintenance medications for recurrent or chronic cases form the basis for effective management. Metagenomic deep sequencing, the development of a herpes vaccine, and cenegermin nerve growth factor offer promise as diagnostic, preventive, and therapeutic options, respectively.
Topics: Animals; Cornea; Humans; Keratitis, Herpetic; Ophthalmic Nerve; Simplexvirus
PubMed: 31567695
DOI: 10.1097/ICU.0000000000000618 -
Neuron Jun 2022Sensitization of trigeminal ganglion neurons contributes to primary headache disorders such as migraine, but the specific neuronal and non-neuronal trigeminal subtypes...
Sensitization of trigeminal ganglion neurons contributes to primary headache disorders such as migraine, but the specific neuronal and non-neuronal trigeminal subtypes that are involved remain unclear. We thus developed a cell atlas in which human and mouse trigeminal ganglia are transcriptionally and epigenomically profiled at single-cell resolution. These data describe evolutionarily conserved and human-specific gene expression patterns within each trigeminal ganglion cell type, as well as the transcription factors and gene regulatory elements that contribute to cell-type-specific gene expression. We then leveraged these data to identify trigeminal ganglion cell types that are implicated both by human genetic variation associated with migraine and two mouse models of headache. This trigeminal ganglion cell atlas improves our understanding of the cell types, genes, and epigenomic features involved in headache pathophysiology and establishes a rich resource of cell-type-specific molecular features to guide the development of more selective treatments for headache and facial pain.
Topics: Animals; Disease Models, Animal; Headache; Humans; Mice; Migraine Disorders; Neurons; Trigeminal Ganglion
PubMed: 35349784
DOI: 10.1016/j.neuron.2022.03.003 -
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 -
The Journal of Headache and Pain Jun 2020Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to... (Review)
Review
Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to the discovery that calcitonin gene-related peptide (CGRP) is a key neuropeptide involved in pain signaling during a migraine attack. CGRP-mediated neuronal sensitization and glutamate-based second- and third-order neuronal signaling may be an important component involved in migraine pain. The activation of several serotonergic receptor subtypes can block the release of CGRP, other neuropeptides, and neurotransmitters, and can relieve the symptoms of migraine. Triptans were the first therapeutics developed for the treatment of migraine, working through serotonin 5-HT receptors. The discovery that the serotonin 1F (5-HT) receptor was expressed in the human trigeminal ganglion suggested that this receptor subtype may have a role in the treatment of migraine. The 5-HT receptor is found on terminals and cell bodies of trigeminal ganglion neurons and can modulate the release of CGRP from these nerves. Unlike 5-HT receptors, the activation of 5-HT receptors does not cause vasoconstriction.The potency of different serotonergic agonists towards 5-HT was correlated in an animal model of migraine (dural plasma protein extravasation model) leading to the development of lasmiditan. Lasmiditan is a newly approved acute treatment for migraine in the United States and is a lipophilic, highly selective 5-HT agonist that can cross the blood-brain barrier and act at peripheral nervous system (PNS) and central nervous system (CNS) sites.Lasmiditan activation of CNS-located 5-HT receptors (e.g., in the trigeminal nucleus caudalis) could potentially block the release of CGRP and the neurotransmitter glutamate, thus preventing and possibly reversing the development of central sensitization. Activation of 5-HT receptors in the thalamus can block secondary central sensitization of this region, which is associated with progression of migraine and extracephalic cutaneous allodynia. The 5-HT receptors are also elements of descending pain modulation, presenting another site where lasmiditan may alleviate migraine. There is emerging evidence that mitochondrial dysfunction might be implicated in the pathophysiology of migraine, and that 5-HT receptors can promote mitochondrial biogenesis. While the exact mechanism is unknown, evidence suggests that lasmiditan can alleviate migraine through 5-HT agonist activity that leads to inhibition of neuropeptide and neurotransmitter release and inhibition of PNS trigeminovascular and CNS pain signaling pathways.
Topics: Animals; Benzamides; Calcitonin Gene-Related Peptide; Humans; Migraine Disorders; Neurons; Piperidines; Pyridines; Receptors, Serotonin; Serotonin Receptor Agonists; Trigeminal Ganglion; Tryptamines; Vasoconstriction; Receptor, Serotonin, 5-HT1F
PubMed: 32522164
DOI: 10.1186/s10194-020-01132-3 -
Oral Diseases Nov 2019The natural history of oral herpes simplex virus type 1 (HSV-1) infection in the immunocompetent host is complex and rich in controversial phenomena, namely the role of... (Review)
Review
The natural history of oral herpes simplex virus type 1 (HSV-1) infection in the immunocompetent host is complex and rich in controversial phenomena, namely the role of unapparent transmission in primary infection acquisition, the high frequency of asymptomatic primary and recurrent infections, the lack of immunogenicity of HSV-1 internalized in the soma (cell body) of the sensory neurons of the trigeminal ganglion, the lytic activity of HSV-1 in the soma of neurons that is inhibited in the sensory neurons of the trigeminal ganglion and often uncontrolled in the other neurons, the role of keratin in promoting the development of recurrence episodes in immunocompetent hosts, the virus-host Nash equilibrium, the paradoxical HSV-1-seronegative individuals who shed HSV-1 through saliva, the limited efficacy of anti-HSV vaccines, and why the oral route of infection is the least likely to produce severe complications. The natural history of oral HSV-1 infection is also a history of symbiosis between humans and virus that may switch from mutualism to parasitism and vice versa. This balance is typical of microorganisms that are highly coevolved with humans, and its knowledge is essential to oral healthcare providers to perform adequate diagnosis and provide proper individual-based HSV-1 infection therapy.
Topics: Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Humans; Stomatitis, Herpetic; Trigeminal Ganglion
PubMed: 31733122
DOI: 10.1111/odi.13234 -
Indian Journal of Dental Research :... 2020This study was aimed at determining the specific signs of close relationship between impacted mandibular third molar (IMTM) root and inferior alveolar nerve (IAN) canal...
OBJECTIVES
This study was aimed at determining the specific signs of close relationship between impacted mandibular third molar (IMTM) root and inferior alveolar nerve (IAN) canal as visualised on digital panoramic radiograph or orthopantomograph (OPG) which should indicate as well as contraindicate the need for cone beam computed tomography (CBCT) imaging based on hierarchical model of Fryback and Thornbury.
MATERIALS AND METHODS
The sample consisted of 120 individuals (200 IMTM) who had undergone OPG as well as CBCT imaging as preoperative radiographic evaluation before surgical extraction. On panoramic radiographs; Rood and Sheehab's radiographic signs of IMTM root and IAN canal, impacted third molar position based on Winter's classification and depth of impaction based on Pell and Gregory's classification were evaluated. On CBCT; presence/absence of corticalization and the status of the buccal and lingual cortices (thinning/perforation) were evaluated. These findings of OPG were compared to CBCT findings to determine the better modality based on hierarchical model of Fryback and Thornbury.
RESULTS
Statistically significant association was found between radiographic signs of Rood and Sheehab such as 'no relation' and 'superimposition' on OPG and presence of corticalization between IMTM root and IAN canal on CBCT. Statistically significant association was also found between 'mesioangular' and 'vertical' positions of Winter's classification as well as 'class 1A' of Pell and Gregory's classification of IMTM on OPG and presence of corticalization on CBCT. CBCT was found to be having lesser variance and greater F value as compared to OPG for evaluation of IMTM.
CONCLUSIONS
On OPG; Rood and Sheehab's radiographic signs such as 'no relation' and 'superimposition', Winter's 'mesioangular' and 'vertical' and Pell and Gregory's 'Class 1A' are not indicative for CBCT examination before surgical extraction is attempted. On OPG; Rood and Sheehab's radiographic signs such as interruption of white line, darkening of root, darkening of canal, deflection of root, narrowing of canal as well as diversion of canal are all frequently associated with absence of corticalization between IMTM root and IAN canal and hence require CBCT examination before surgical extraction is attempted so that post-operative neurological complications can be minimised. Also, Winter's horizontal, distoangular and others as well Pell and Gregory's classes 1B,1C,2A,2B,2C,3A,3B,3C are indicative for CBCT examination before surgical extraction is attempted. Fryback and Thornbury model-based comparison proves that CBCT is a better radiographic modality as compared to OPG for evaluation of IMTM relation with IAN canal.
Topics: Cone-Beam Computed Tomography; Humans; Mandible; Mandibular Nerve; Molar, Third; Radiography, Panoramic; Tooth Extraction; Tooth, Impacted
PubMed: 32246689
DOI: 10.4103/ijdr.IJDR_540_18 -
The Pan African Medical Journal 2019
Topics: Administration, Oral; Antiviral Agents; Drug Therapy, Combination; Earache; Facial Paralysis; Glucocorticoids; Herpes Zoster Oticus; Herpesvirus 3, Human; Humans; Hypesthesia; Male; Middle Aged; Prednisolone; Skin Diseases, Vesiculobullous; Trigeminal Nerve; Valacyclovir; Varicella Zoster Virus Infection
PubMed: 32180875
DOI: 10.11604/pamj.2019.34.201.19207