Periodic Reporting for period 2 - SENSO-CIGUA (Neurobiology of sensory disturbances induced by ciguatoxins)
Période du rapport: 2022-09-01 au 2023-08-31
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).
In conclusion of the action, the project, which achieved most of its specific objectives, contributed to a significant advance in the state of the art in the field. Using an assay capable of distinguishing between itch and pain-related behaviours, we characterized the behaviours induced by a range of (sub)nanomolar doses of ciguatoxin administered in direct contact with sensory nerves, and studied the involvement of molecular actors. The project also expanded the available knowledge about the subpopulations of sensory neurons activated by ciguatoxin and its ability to sensitize sensory pathways, for example involved in pain and itch.
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).
In conclusion of the action, the project, which achieved most of its specific objectives, contributed to a significant advance in the state of the art in the field. Using an assay capable of distinguishing between itch and pain-related behaviours, we characterized the behaviours induced by a range of (sub)nanomolar doses of ciguatoxin administered in direct contact with sensory nerves, and studied the involvement of molecular actors. The project also expanded the available knowledge about the subpopulations of sensory neurons activated by ciguatoxin and its ability to sensitize sensory pathways, for example involved in pain and itch.
We administered ciguatoxin intradermally to normal-type mice and characterized the induced behaviours. By using mice in which ion channels, receptors or cells involved in pain and itch were lacking or blocked, we assessed the involvement of these molecular or cellular 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.
Results of the project have been presented at the following international/national conferences or congresses:
• Annual conference of the research network Phycotox 2023, Nantes, France
• Congrès Annuel de Recherche Dermatologique CARD 2023, Brest, France
• International Congress on Neuropathic Pain of IASP Neuropathic Pain Special Interest Group (NeuPSIG) 2023, Lisbon, Portugal
• 12th World Congress on Itch 2023, Miami, United States of America
• American Romanian Academy of Arts and Sciences 2023 (44th ARA Congress), Timisoara, Romania
• 19th Symposium of the French Pain Research Network 2024, Nice, France
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.
Results of the project have been presented at the following international/national conferences or congresses:
• Annual conference of the research network Phycotox 2023, Nantes, France
• Congrès Annuel de Recherche Dermatologique CARD 2023, Brest, France
• International Congress on Neuropathic Pain of IASP Neuropathic Pain Special Interest Group (NeuPSIG) 2023, Lisbon, Portugal
• 12th World Congress on Itch 2023, Miami, United States of America
• American Romanian Academy of Arts and Sciences 2023 (44th ARA Congress), Timisoara, Romania
• 19th Symposium of the French Pain Research Network 2024, Nice, France
The socio-economic impacts of ciguatera are numerous, given the global incidence of this disease, especially in regions where seafood is the dominant diet. This project aims to deepen knowledge on the neural mechanisms of ciguatera sensory disturbances, in order to ultimately target these mechanisms to develop specific therapies. Treating ciguatera sensory disturbances effectively and specifically could reduce the socio-economic impacts linked to the health of populations: symptoms affecting the quality of life, sometimes very lastingly, and their economic consequences (e.g. work stoppage).