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Neurobiology of sensory disturbances induced by ciguatoxins

Periodic Reporting for period 1 - SENSO-CIGUA (Neurobiology of sensory disturbances induced by ciguatoxins)

Período documentado: 2021-09-01 hasta 2022-08-31

Ciguatera is the most prevalent human seafood poisoning in the world. It is caused by eating seafood containing ciguatoxins, which originate from marine microalgae of the genera Gambierdiscus or Fukuyoa. Ciguatera has affected tropical and subtropical regions for centuries. Recently, the responsible microalgae have reached more temperate climatic zones, including European countries, where cases of ciguatera caused by local fish are reported. The most prevalent and characteristic symptoms of ciguatera are sensory disturbances including unpleasant tingling and painful burning sensations called paresthesiae and dysesthesiae, especially when the skin or mucosae are in contact with cold or cool air, water, drink or food. Itch (pruritus), the unpleasant sensation evoking the urgent need to scratch, is another hallmark symptom of ciguatera. In addition, pain localized in the head (migraine), digestive tract, joints, muscles or teeth are commonly described. All of these ciguatoxin-induced abnormal sensations come from a common cellular target, namely sensory neurons.

There is no specific or effective treatment for ciguatera sensory disturbances. They greatly affect the quality of life, especially when they last for weeks, months or even years, associated with chronic fatigue. In areas endemic for ciguatera, the dietary eviction and marketing ban of the most incriminated seafood species make ciguatera a significant public health and economic concern.

The overall objective of the SENSO-CIGUA project is to better understand the neural mechanisms by which ciguatoxins induce these sensory disturbances in order to ultimately find out bases for specific treatment(s).
We administered ciguatoxin intradermally to normal-type mice and characterized the induced behaviours. By using mice in which ion channels or receptors involved in pain and itch were lacking or blocked, we assessed the involvement of these molecular components in ciguatoxin-evoked behaviours.

We also sought to identify subpopulations of sensory neurons targeted by ciguatoxin, whose better understanding could contribute to increasing knowledge of the neural mechanisms of ciguatera and beyond, abnormal cold-induced pain and itch.

We also investigated in mice and sensory neurons the ability of ciguatoxin to sensitize -i.e. to increase responses or decrease response thresholds of- receptors and ion channels involved in pain and itch.
By deepening knowledge on the neural mechanisms of ciguatera sensory disturbances, this project could provide bases for the development of targeted therapies.

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