Effects of Capsaicin and Heat on Central Sensitization in Manduca Sexta
Angus Hamilton, Josiah McGrew, Octavio Manriquez, Sathya Correa
Department of Biology
Faculty Supervisor: Megumi Fuse
Chronic pain is an ongoing problem in this country, and with overdose deaths continuing to rise, there is a great need for an alternate solution. The hornworm, Manduca sexta, is becoming a model for studying ongoing sensitivity to pain after mechanical injury. But even though much of the chronic pain experienced in humans arises from thermal injury, this has not yet been studied in our insect model. Vertebrates and invertebrates both sense thermal stimuli through a variety of TRP receptors. Many chemical ligands, like capsaicin, also work through these channels, simulating thermal nociception in absence of noxious temperatures. M. sexta may prove a valuable model for testing this thermal and chemical sensitization as it possesses TRPA channels to sense heat similarly to Drosophila melanogaster, but from our phylogenetics it seems to lack the TRPV1 channels that capsaicin usually acts through. We tested the response to capsaicin in M. sexta and found that it sensitizes them in a dose-dependent manner, while the TRPV1 channel inhibitor, capsazepine, was largely ineffective at preventing sensitization. Heat also appears to sensitize the insect, verifying the multimodal nature of some M. sexta nociceptors. We further conducted a phylogenetic analysis, where the TRPV1 channels that capsaicin usually acts through cannot be found in M. sexta. We are therefore also testing whether the TRPA1 channel inhibitor HC-030031 can block the effects of capsaicin and laser-based heat, as capsaicin has been shown to activate TRPA1 channels in canine kidney cells in absence of TRPV1 channels. This data will be discussed in the context of using M. sexta as a model for novel pain management strategies.