Antinociceptive Activity of Vanilloids in Caenorhabditis elegans is Mediated by the Desensitization of the TRPV Channel OCR-2 and Specific Signal Transduction Pathways

• Published in: Neurochemical research Vol. 48; no. 6; pp. 1900 - 1911
• Main Authors: Nkambeu, Bruno, Salem, Jennifer Ben, Beaudry, Francis
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2023; Springer Nature B.V
• Subjects: Analgesics; Analgesics - chemistry; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biosynthesis; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - metabolism; Calcium ions; Capsaicin; Capsaicin - pharmacology; Capsaicin receptors; Catalysis; Cell Biology; Desensitization; Eugenol; Eugenol - pharmacology; Nematodes; Nerve Tissue Proteins - metabolism; Neurochemistry; Neurology; Neurosciences; Original Paper; Pain; Pain perception; Phenotypes; Proteins; Proteomes; Proteomics; Receptors; Sensory transduction; Signal generation; Signal Transduction; Signaling; Transient receptor potential proteins; TRPV Cation Channels - metabolism; Wnt protein; Nociception; Transient receptor potential cation channel; Capsaicin; Eugenol; Mass spectrometry; Proteomics; Caenorhabditis elegans
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-023-03876-1

Vanilloids, including capsaicin and eugenol, are ligands of transient receptor potential channel vanilloid subfamily member 1 (TRPV1). Prolonged treatment with vanilloids triggered the desensitization of TRPV1, leading to analgesic or antinociceptive effects. Caenorhabditis elegans ( C. elegans ) is a model organism expressing vanilloid receptor orthologs (e.g., OSM-9 and OCR-2) that are associated with behavioral and physiological processes, including sensory transduction. We have shown that capsaicin and eugenol hamper the nocifensive response to noxious heat in C. elegans . The objective of this study was to perform proteomics to identify proteins and pathways responsible for the induced phenotype and to identify capsaicin and eugenol targets using a thermal proteome profiling (TPP) strategy. The results indicated hierarchical differences following Reactome Pathway enrichment analyses between capsaicin- and eugenol-treated nematodes. However, both treated groups were associated mainly with signal transduction pathways, energy generation, biosynthesis and structural processes. Wnt signaling, a specific signal transduction pathway, is involved following treatment with both molecules. Wnt signaling pathway is noticeably associated with pain. The TPP results show that capsaicin and eugenol target OCR-2 but not OSM-9. Further protein–protein interaction (PPI) analyses showed other targets associated with enzymatic catalysis and calcium ion binding activity. The resulting data help to better understand the broad-spectrum pharmacological activity of vanilloids.