Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat

Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and the TRPV1 is activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32-35 °C) following a sustained exposition. Also, the effect was reversed 6 h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed.