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State-of-the-Art Research in Trigeminal Nerve Stimulation

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 7659

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Special Issue Editor

Dr. Beniamina Mercante

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Guest Editor

Department of Biomedical Sciences, University of Sassari, Sassari, Italy
Interests: neuromodulation; trigeminal nerve stimulation; translational neuroscience; neurobiology and brain physiology; cognitive process

Special Issue Information

Dear Colleagues,

Trigeminal nerve contains sensory axons that send tactile and nociceptive information from the face and anterior region of the external ear to the central nervous system as well as descending motor axons that innervate masticatory muscles. Afferent projections from the trigeminal ganglion ascend to the trigeminal nuclei in the brainstem and project bilaterally to multiple brainstem nuclei and to forebrain structures. Owing to its extensive connections within the central nervous system, the trigeminal nerve is considered strategic for influencing the activity of both cortical and subcortical structures. Peripheral stimulation of trigeminal nerve (TNS) has been proposed as a treatment option for different neurologic and neuropsychiatric disorders. However, despite increasing clinical use, the anatomo-functional correlates of TNS have not been clearly elucidated thus hampering the development of standardized stimulation protocols, providing demonstrable therapeutic efficacy. Contributions to this special issue shall focus on the mechanisms of TNS, its effects on physiological conditions such as mood, sleep and cognition, as well as its application in preclinical and clinical studies of neurological and neuropsychiatric diseases.

Authors are invited to submit their original research, communications, and review articles to Biomedicines.

Dr. Beniamina Mercante
Guest Editor

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Keywords

trigeminal nerve
trigeminal nerve stimulation
neuromodulation
neuropsychiatric disorders
cognition

Published Papers (4 papers)

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Research

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14 pages, 2802 KiB

Open AccessArticle

Intracellular cAMP Signaling Pathway via G_s Protein-Coupled Receptor Activation in Rat Primary Cultured Trigeminal Ganglion Cells

by Yuki Kunioku, Maki Kimura, Takehito Ouchi, Kenichi Fukuda and Yoshiyuki Shibukawa

Biomedicines 2023, 11(9), 2347; https://doi.org/10.3390/biomedicines11092347 - 23 Aug 2023

Cited by 2 | Viewed by 1150

Abstract

G protein-coupled receptors in trigeminal ganglion (TG) neurons are often associated with sensory mechanisms, including nociception. We have previously reported the expression of P2Y₁₂ receptors, which are G_i protein-coupled receptors, in TG cells. Activating P2Y₁₂ receptors decreased the intracellular free Ca²⁺ concentration ([Ca²⁺]_i). This indicated that intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) levels can mediate Ca²⁺ signaling in TG cells. Here, we report more extensive-expression patterns of G_s protein-coupled receptors in primary cultured TG neurons isolated from 7-day-old newborn Wistar rats and further examine the roles of these receptors in cAMP signaling using the BacMam sensor in these neurons. To identify TG neurons, we also measured [Ca²⁺]_i using fura-2 in TG cells and measured intracellular cAMP levels. TG neurons were positive for Gα_s protein-coupled receptors, beta-2 adrenergic (β₂), calcitonin gene-related peptide (CGRP), adenosine A_2A (A_2A), dopamine 1 (D1), prostaglandin I₂ (IP), and 5-hydroxytriptamine 4 (5-HT₄) receptor. Application of forskolin (FSK), an activator of adenylyl cyclase, transiently increased intracellular cAMP levels in TG neurons. The application of a phosphodiesterase inhibitor augmented the FSK-elicited intracellular cAMP level increase. These increases were significantly suppressed by the application of SQ22536, an adenylyl cyclase inhibitor, in TG neurons. Application of agonists for β₂, CGRP, A_2A, D1-like, IP, and 5-HT₄ receptors increased intracellular cAMP levels. These increases were SQ22536-sensitive. These results suggested that TG neurons express β₂, CGRP, A_2A, D1, IP, and 5-HT₄ receptors, and the activations of these Gα_s protein-coupled receptors increase intracellular cAMP levels by activating adenylyl cyclase. Full article

(This article belongs to the Special Issue State-of-the-Art Research in Trigeminal Nerve Stimulation)

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24 pages, 10159 KiB

Open AccessArticle

Trigeminal Stimulation and Visuospatial Performance: The Struggle between Chewing and Trigeminal Asymmetries

by Maria Paola Tramonti Fantozzi, Vincenzo De Cicco, Paola d’Ascanio, Enrico Cataldo, Davide De Cicco, Luca Bruschini, Massimo Barresi, Ugo Faraguna and Diego Manzoni

Biomedicines 2023, 11(8), 2307; https://doi.org/10.3390/biomedicines11082307 - 19 Aug 2023

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Abstract

Chewing improves visuospatial performance through locus coeruleus (LC) activation. The effects of bilateral and unilateral mastication were investigated in subjects showing different degrees of asymmetry in masseter electromyographic (EMG) activity during clenching and in pupil size at rest (anisocoria), which is a proxy of LC imbalance. Correlations between performance changes and asymmetry values were found in males, but not in females. Among males, subjects with low asymmetry values (balanced-BAL) were more sensitive than those with high asymmetry values (imbalanced-IMB) to bilateral and unilateral chewing on the side with higher EMG activity (hypertonic). The opposite was true for hypotonic side chewing. BAL subjects were sensitive to unilateral chewing on both sides, while in IMB subjects, hypertonic side chewing did not influence performance in either males or females. Bilateral chewing elicited larger effects in BAL subjects than in IMB subjects, exceeding the values predicted from unilateral chewing in both groups. Finally, pupil size and anisocoria changes elicited by chewing were correlated with asymmetry values, independent of sex. Data confirmed the facilitation of visuospatial performance exerted by chewing. Trigeminal asymmetries modulate the chewing effects, making occlusal rebalancing an appropriate strategy to improve performance. Full article

(This article belongs to the Special Issue State-of-the-Art Research in Trigeminal Nerve Stimulation)

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Review

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14 pages, 630 KiB

Open AccessReview

Cognitive Functions following Trigeminal Neuromodulation

by Beniamina Mercante, Paolo Enrico and Franca Deriu

Biomedicines 2023, 11(9), 2392; https://doi.org/10.3390/biomedicines11092392 - 27 Aug 2023

Viewed by 1302

Abstract

Vast scientific effort in recent years have been focused on the search for effective and safe treatments for cognitive decline. In this regard, non-invasive neuromodulation has gained increasing attention for its reported effectiveness in promoting the recovery of multiple cognitive domains after central nervous system damage. In this short review, we discuss the available evidence supporting a possible cognitive effect of trigeminal nerve stimulation (TNS). In particular, we ask that, while TNS has been widely and successfully used in the treatment of various neuropsychiatric conditions, as far as research in the cognitive field is concerned, where does TNS stand? The trigeminal nerve is the largest cranial nerve, conveying the sensory information from the face to the trigeminal sensory nuclei, and from there to the thalamus and up to the somatosensory cortex. On these bases, a bottom-up mechanism has been proposed, positing that TNS-induced modulation of the brainstem noradrenergic system may affect the function of the brain networks involved in cognition. Nevertheless, despite the promising theories, to date, the use of TNS for cognitive empowering and/or cognitive decline treatment has several challenges ahead of it, mainly due to little uniformity of the stimulation protocols. However, as the field continues to grow, standardization of practice will allow for data comparisons across studies, leading to optimized protocols targeting specific brain circuitries, which may, in turn, influence cognition in a designed manner. Full article

(This article belongs to the Special Issue State-of-the-Art Research in Trigeminal Nerve Stimulation)

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28 pages, 15267 KiB

Open AccessReview

Trigeminal Function in Sino-Nasal Health and Disease

by Dennis Shusterman

Biomedicines 2023, 11(7), 1778; https://doi.org/10.3390/biomedicines11071778 - 21 Jun 2023

Cited by 2 | Viewed by 3604

Abstract

The upper airway (nasal passages, paranasal sinuses, pharynx, and glottis) provides the sentinel portion of the human respiratory tract, with the combined senses of olfaction (cranial nerve I) and trigeminal sensation (cranial nerve V) signaling the quality of inspired air. Trigeminal function also complements the sense of taste (in turn mediated by cranial nerves VII, IX and X), and participates in the genesis of taste aversions. The ability of trigeminal stimulation in the upper aero-digestive tract to trigger a variety of respiratory and behavioral reflexes has long been recognized. In this context, the last three decades has seen a proliferation of observations at a molecular level regarding the mechanisms of olfaction, irritation, and gustation. Concurrently, an ever-widening network of physiological interactions between olfaction, taste, and trigeminal function has been uncovered. The objective of this review is to summarize the relatively recent expansion of research in this sub-field of sensory science, and to explore the clinical and therapeutic implications thereof. Full article

(This article belongs to the Special Issue State-of-the-Art Research in Trigeminal Nerve Stimulation)

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