Neurological Disturbances of Ciguatera Poisoning: Clinical Features and Pathophysiological Basis

Ciguatera fish poisoning (CFP), the most prevalent seafood poisoning worldwide, is caused by the consumption of tropical and subtropical fish contaminated with potent neurotoxins called ciguatoxins (CTXs). Ciguatera is a complex clinical syndrome in which peripheral neurological signs predominate in the acute phase of the intoxication but also persist or reoccur long afterward. Their recognition is of particular importance in establishing the diagnosis, which is clinically-based and can be a challenge for physicians unfamiliar with CFP. To date, no specific treatment exists. Physiopathologically, the primary targets of CTXs are well identified, as are the secondary events that may contribute to CFP symptomatology. This review describes the clinical features, focusing on the sensory disturbances, and then reports on the neuronal targets and effects of CTXs, as well as the neurophysiological and histological studies that have contributed to existing knowledge of CFP neuropathophysiology at the molecular, neurocellular and nerve levels

Release of neuropeptides from a neuro-cutaneous co-culture model: a novel in vitro model for studying sensory effects of ciguatoxins

Ciguatoxins are the major toxins responsible for ciguatera fish poisoning, a disease dominated by muco-cutaneous sensory disorders including paresthesiae, cold dysesthesia and pruritus. While the ciguatoxins are well known to target voltage-gated sodium channels (VGSCs), the ensuing molecular mechanisms underlying these sensory disorders remain poorly understood. In this study, we propose a primary sensory neuron-keratinocyte co-culture as an appropriate model to study the neuro-cutaneous effects of ciguatoxins. Using this model, we show for the first time that nanomolar concentrations of Pacific ciguatoxin-2 (P-CTX-2) induced a VGSC-dependent release of substance P (SP) and calcitonin gene-related peptide (CGRP). As these neuropeptides are known mediators of pain and itch sensations, the ciguatoxin-induced sensory disturbances in ciguatera fish poisoning may involve the release of these neuropeptides. We further determined time- and P-CTX-2 concentration-dependence of the release of SP and CGRP from the co-culture model. Moreover, we highlighted the influence of extracellular calcium on the release of neuropeptides elicited by P-CTX-2. These findings underline the usefulness of this novel in vitro model for studying the cellular and molecular mechanisms of the neuro-cutaneous effects of ciguatoxins, which may assist with identifying potential therapeutics for ciguatera fish poisoning

CHRONIC ITCH: EMERGING TREATMENTS FOLLOWING NEW RESEARCH CONCEPTS

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Guidance Level for Brevetoxins in French Shellfish

Brevetoxins (BTXs) are marine biotoxins responsible for neurotoxic shellfish poisoning (NSP) after ingestion of contaminated shellfish. NSP is characterized by neurological, gastrointestinal and/or cardiovascular symptoms. The main known producer of BTXs is the dinoflagellate Karenia brevis, but other microalgae are also suspected to synthesize BTX-like compounds. BTXs are currently not regulated in France and in Europe. In November 2018, they have been detected for the first time in France in mussels from a lagoon in the Corsica Island (Mediterranean Sea), as part of the network for monitoring the emergence of marine biotoxins in shellfish. To prevent health risks associated with the consumption of shellfish contaminated with BTXs in France, a working group was set up by the French Agency for Food, Environmental and Occupational Health & Safety (Anses). One of the aims of this working group was to propose a guidance level for the presence of BTXs in shellfish. Toxicological data were too limited to derive an acute oral reference dose (ARfD). Based on human case reports, we identified two lowest-observed-adverse-effect levels (LOAELs). A guidance level of 180 µg BTX-3 eq./kg shellfish meat is proposed, considering a protective default portion size of 400 g shellfish meat

PAR2, Keratinocytes, and Cathepsin S Mediate the Sensory Effects of Ciguatoxins Responsible for Ciguatera Poisoning

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Salivary metabolome indicates a shift in tyrosine metabolism in patients with burning mouth syndrome: a prospective case–control study

International audienceThe pathophysiology of primary burning mouth syndrome (BMS) remains controversial. Targeted analyses or "omics" approach of saliva provide diagnostic or pathophysiological biomarkers. This pilot study's primary objective was to explore the pathophysiology of BMS through a comparative analysis of the salivary metabolome among 26 BMS female cases and 25 age- and sex-matched control subjects. Secondary objectives included comparative analyses of inflammatory cytokines, neuroinflammatory markers, and steroid hormones among cases and control subjects, and among BMS patients according to their clinical characteristics. Salivary metabolome, neuroinflammatory markers, cytokines, and steroids were, respectively, analysed by liquid chromatography coupled with mass spectrometry, ELISA and protease activity assay, and multiparametric Luminex method. Among the 166 detected metabolites, univariate analysis did not find any discriminant metabolite between groups. Supervised multivariate analysis divided patients into 2 groups with an accuracy of 60% but did not allow significant discrimination (permutation test, P = 0.35). Among the metabolites contributing to the model, 3 belonging to the tyrosine pathway ( l -dopa, l -tyrosine, and tyramine) were involved in the discrimination between cases and control subjects, and among BMS patients according to their levels of pain. Among the detectable molecules, levels of cytokines, steroid hormones, and neuroinflammatory markers did not differ between cases and control subjects and were not associated with characteristics of BMS patients. These results do not support the involvement of steroid hormones, inflammatory cytokines, or inflammatory neurogenic mediators in the pathophysiology of pain in BMS, whereas the observed shift in tyrosine metabolism may indicate an adaptative response to chronic pain or an impaired dopaminergic transmission

Major Role for TRPV1 and InsP3R in PAR2-Elicited Inflammatory Mediator Production in Differentiated Human Keratinocytes

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Keratinocytes Communicate with Sensory Neurons via Synaptic‐like Contacts

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