Using the nematode C. elegans to assay the effectiveness of novel anti‐nociceptive compounds targeting transient receptor potential vanilloid 1 (TRPV1) channels

TRPV1 channels are expressed in nociceptive neurons and are involved in sensing noxious thermal and chemical stimuli. Because of their roles in the pain pathway, these channels have emerged as important therapeutic targets for the development of new analgesics. Capsaicin, the pungent ingredient in hot chili peppers, is a known agonist of TRPV1. Transgenic C. elegans nematodes expressing rat TRPV1 in sensory neurons exhibit a reversal response upon exposure to capsaicin. Pre‐incubation of the worms with capsazepine, a selective TRPV1 antagonist, potently blocks their response to capsaicin. Thus, we are using capsaicin‐induced reversal behavior as an assay to test the effectiveness of novel TRPV1 ligands. Data on the effectiveness of N‐cyanoguanidine analogs of capsaicin, capsazepine, SB 366791 and AMG 9810 will be presented.