Abstract
Ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning syndromes are induced by the consumption of seafood contaminated by ciguatoxins and brevetoxins. Both toxins cause sensory symptoms such as paresthesia, cold dysesthesia and painful disorders. An intense pruritus, which may become chronic, occurs also in CFP. No curative treatment is available and the pathophysiology is not fully elucidated. Here we conducted single-cell calcium video-imaging experiments in sensory neurons from newborn rats to study in vitro the ability of Pacific-ciguatoxin-2 (P-CTX-2) and brevetoxin-1 (PbTx-1) to sensitize receptors and ion channels, (i.e., to increase the percentage of responding cells and/or the response amplitude to their pharmacological agonists). In addition, we studied the neurotrophin release in sensory neurons co-cultured with keratinocytes after exposure to P-CTX-2. Our results show that P-CTX-2 induced the sensitization of TRPA1, TRPV4, PAR2, MrgprC, MrgprA and TTX-r NaV channels in sensory neurons. P-CTX-2 increased the release of nerve growth factor and brain-derived neurotrophic factor in the co-culture supernatant, suggesting that those neurotrophins could contribute to the sensitization of the aforementioned receptors and channels. Our results suggest the potential role of sensitization of sensory receptors/ion channels in the induction or persistence of sensory disturbances in CFP syndrome.
Highlights
We studied the ability of P-CTX-2 and PbTx-1 to sensitize several receptors and ion channels in dorsal root ganglion (DRG) neurons using single-cell calcium video imaging
After pretreatment with PbTx-1, P-CTX-2 or vehicle controls for 20 h, we assessed the change in the calcium response to the specific agonist of each sensory receptor induced by the toxins compared with their vehicle controls
These results suggest a sensitization of transient receptor potential A1 (TRPA1) by P-CTX-2 and PbTx-1 in sensory neurons
Summary
Ciguatera fish poisoning (CFP) is a syndrome consecutive to an oral consumption of CTX contaminated fish [6,7]. CFP includes gastrointestinal symptoms (e.g., diarrhea, nausea, vomiting and abdominal pain), typical sensory disturbances (e.g., paresthesia, cold dysesthesia, pruritus, dental pain and myalgia) and in the most severe cases, cardiovascular signs [7,11,12,13,14,15,16,17,18]. The intense and disabling sensory disturbances of CFP [11,19], can persist several days, weeks or even years after the toxic meal ingestion. Sensory symptoms reoccur or are exacerbated after consumption of alcohol, certain foods or after physical exercise [6,20]
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