Journal of Vestibular Research - Volume 23, issue 3

Authors: Chabbert, Christian

Article Type: Research Article

Abstract: Recent epidemiological investigations have highlighted the high prevalence of vestibular dysfunctions in the adult population and its association with aging. Despite a large and unmet medical need, the pharmaceutical options of targeted and efficient drugs to reduce the symptoms associated with vestibular deficits remains largely insufficient. This special issue of the Journal of Vestibular Research is devoted to the session: New insights on vestibular neuropharmacology: From bench to bedside, that was organized at the 2012 Midwinter Meeting of the Association of Research in Otolaryngology. This special issue intends 1. to emphasize the current state of the …medical need for potent pharmacological treatments of vestibular deficits while highlighting questions regarding the molecular targets, the therapeutic window and the role of pharmacological treatment versus physiotherapy; 2. to give an overview of the fundamental mechanisms of vestibular system function and the mechanism of action of the drugs currently used in the treatment of vestibular disorders and 3. to present recent discoveries in basic research, that may lead to future drug identification to efficiently alleviate the vertigo crisis and protect the vestibule. This theme should target a broad audience ranging from ENT clinicians to scientists, including pharmacologists and pharmacists. Show more

DOI: 10.3233/VES-130495

Citation: Journal of Vestibular Research, vol. 23, no. 3, pp. 107-111, 2013

Authors: Agrawal, Yuri | Ward, Bryan K. | Minor, Lloyd B.

Article Type: Research Article

DOI: 10.3233/VES-130498

Citation: Journal of Vestibular Research, vol. 23, no. 3, pp. 113-117, 2013

Authors: Soto, Enrique | Vega, Rosario | Seseña, Emmanuel

Article Type: Research Article

Abstract: This work reviews the neuropharmacology of the vestibular system, with an emphasis on the mechanism of action of drugs used in the treatment of vestibular disorders. Clinicians are confronted with a rapidly changing field in which advances in the knowledge of ionic channel function and synaptic transmission mechanisms have led to the development of new scientific models for the understanding of vestibular dysfunction and its management. In particular, there have been recent advances in our knowledge of the fundamental mechanisms of vestibular system function and of drug action. In this work, drugs acting on vestibular system have been grouped into …two main categories according to their primary mechanisms of action: those with effects on neurotransmitters and neuromodulators dynamics and those that act on voltage-gated ion channels. Particular attention is given in this review to drugs that may provide additional insight into the pathophysiology of vestibular diseases. The critical analysis of the literature reveals that there is a significant lack of information defining the real utility of diverse drugs used in clinical practice. The development of basic studies addressing drug actions at the molecular, cellular and systems level, combined with reliable and well controlled clinical trials, would provide the scientific basis for new strategies for the treatment of vestibular disorders. Show more

Keywords: Inner ear, vertigo, dizziness, Ménière's disease, vestibular nuclei, hair cells, excitatory amino acids, antihistaminic, neuropeptides, ionic channels

DOI: 10.3233/VES-130494

Citation: Journal of Vestibular Research, vol. 23, no. 3, pp. 119-137, 2013

Authors: Lacour, Michel

Article Type: Research Article

Abstract: Betahistine dihydrochloride (betahistine) is currently used in the management of vertigo and vestibular pathologies with different aetiologies. The main goal of this review is to clarify the mechanisms of action of this drug, responsible for the symptomatic relief of vertigo and the improvement of vestibular compensation. The review starts with a brief summary recalling the role of histamine as a neuromodulator/neurotransmitter in the control of the vestibular functions, and the role of the histaminergic system in vestibular compensation. Then are presented data recorded in animal models demonstrating that betahistine efficacy can be explained by mechanisms targeting the histamine receptors (HRs) …at three different levels: the vascular tree, with an increase of cochlear and vestibular blood flow involving the H1R; the central nervous system, with an increase of histamine turnover implicating the H3R, and the peripheral labyrinth, with a decrease of vestibular input implying the H3R/H4R. Clinical data from vestibular loss patients show the impact of betahistine treatment for the long-term control of vertigo, improvement of balance and quality of life that can be explained by these mechanisms of action. However, two conditions, at least, are required for reaching the betahistine therapeutic effect: the dose and the duration of treatment. Experimental and clinical data supporting these requirements are exposed in the last part of this review. Show more

Keywords: Vertigo, vestibular compensation, histamine receptors, betahistine

DOI: 10.3233/VES-130496

Citation: Journal of Vestibular Research, vol. 23, no. 3, pp. 139-151, 2013

Authors: Wersinger, Eric | Gaboyard-Niay, Sophie | Travo, Cécile | Soto, Enrique | Baez, Adriana | Vega, Rosario | Brugeaud, Aurore | Chabbert, Christian

Article Type: Research Article

Abstract: Vestibular disorders display high prevalence and can severely impact the daily life. However, pharmacological options that would efficiently relieve the vertigo symptoms without side effects are still lacking. In the present review we briefly review the common history of histamine receptor modulation and the pharmacological therapy of vestibular disorders. We also discuss the recent demonstration of Histamine H4 Receptor mRNAs expression in Scarpa's ganglion of mammal and the potential use of specific H4R antagonists as vestibulomodulators. Additional original data confirm the expression of H4R proteins in the rat vestibular primary neurons, the neuromodulatory properties of specific H4R antagonists in vitro …(inhibition of vestibular neuron excitability) as well as their efficacy to decrease vestibular deficits induced in different in animal models. Show more

Keywords: Vestibule, vertigo, histamine receptors, Ménière's disease, vestibular neurons, hair cells

DOI: 10.3233/VES-130493

Citation: Journal of Vestibular Research, vol. 23, no. 3, pp. 153-159, 2013

Authors: Jordan, Paivi M. | Parks, Xiaorong Xu | Contini, Donatella | Holt, J. Chris

Article Type: Research Article

Abstract: The vestibular labyrinth of nearly every vertebrate class receives a prominent efferent innervation that originates in the brainstem and ends as bouton terminals on vestibular hair cells and afferents in each end organ. Although the functional significance of this centrifugal pathway is not well understood, it is clear that efferent neurons, when electrically stimulated under experimental conditions, profoundly impact vestibular afferent discharge. Effects range from chiefly excitation in fish and mammalian vestibular afferents to a more heterogeneous mixture of inhibition and/or excitation in amphibians, reptiles, and birds. What accounts for these diverse response properties? Recent cellular and pharmacological characterization of …efferent synaptic mechanisms in turtle offers some insight. In the turtle posterior crista, vestibular efferent neurons are predominantly cholinergic and the effects of efferent stimulation on vestibular afferent discharge can be ascribed to three distinct signaling pathways: (1) Hyperpolarization of type II hair cells mediated by α9/α10-nAChRs and SK-potassium channels; (2) Depolarization of bouton and calyx afferents via α4β2*-containing nAChRs; and (3) A slow excitation of calyx afferents attributed to muscarinic AChRs. In this review, we discuss the evidence for these pathways in turtle and speculate on their role in mammalian vestibular efferent actions where synaptic mechanisms are largely unknown. Show more

Keywords: Vestibular efferent, vestibular afferent, acetylcholine, nicotinic, muscarinic

DOI: 10.3233/VES-130492

Citation: Journal of Vestibular Research, vol. 23, no. 3, pp. 161-175, 2013

Authors: Dyhrfjeld-Johnsen, Jonas | Gaboyard-Niay, Sophie | Broussy, Audrey | Saleur, Aurélie | Brugeaud, Aurore | Chabbert, Christian

Article Type: Research Article

Abstract: Vestibular neuritis is a neuroinflammatory, peripheral vestibular pathology leading to chronic deficits and long-term disability. While current corticosteroid-based therapy does not appear to positively influence the long term outcome for the patient, a recent clinical pilot study suggested a functional vestibuloprotective effect of the anti-emetic ondansetron in the treatment of vestibular neuritis. We here demonstrate that systemic post-insult administration of ondansetron in a novel rat model of severe excitotoxic vestibular insult reproduces the clinically demonstrated functional benefits. This ondansetron-conferred reduction of functional deficits stems from the protection of synapses between sensory hair cells and primary neurons from excitotoxically induced lesion.

Keywords: Vestibule, excitoxicity, neuritis, ondansetron, vertigo, functional deficit, nystagmus

DOI: 10.3233/VES-130483

Citation: Journal of Vestibular Research, vol. 23, no. 3, pp. 177-186, 2013