Resiniferatoxin (RTX) is a product found the Resiniferous Euphorbia plant and is also a potent analogue of capsaicin, a natural chemical compound that produces a painful burning sensation but also an analgesic effect following the desensitization of vanilloid receptors (TRPV1). Caenorhabditis elegans (C. elegans) is a nematode with 1/3 of its cells being neurons. Moreover, C. elegans expresses vanilloid receptors, similar in other species, which are essential for the propagation of the nociceptive (pain) message.
goal
Jennifer Ben Salem, Francis Beaudry et al. hypothesized that RTX interacts with TRPV1 ortholog channels in a similar way to capsaicin and prolonged exposure to RTX impairs the organism’s response to noxious heat. The objective of this study was to identify the relationship between the exposure and the response to RTX by analyzing the heat avoidance behavior of C. elegans. The research team also wanted to determine the proteins and mechanisms responsible for this phenomenon.
methodology
After RTX exposure, the nematodes were placed on petri dishes divided into quadrants for heat stimulation (32°C – 35°C). The heat avoidance index was used to determine the behavior of each group. Once the nematodes were exposed (or not) to RTX, the protein level was measured using proteomic analysis and mass spectrometry.
main findings
RTX significantly decreases the sensitivity to noxious heat following prolonged activation and desensitization of a vanilloid receptor (OSM-3), which is a different receptor on which capsaicin acts. This effect was reversed six hours after RTX exposure. Proteomic and bioinformatic analyses relealed that the effects observed with RTX may be related to the ?-catenin-independent Wnt signaling pathway.
take home message
These data showed for the first time that RTX can impar the response of C. elegans to noxious heat. The identified molecular mechanisms by which RTX acts are related to depression, anxiety and apathy, clinically well-established comorbidities with persistent pain.
