Meeting Abstract
Nociception is the neural process that underlies responses to threatening stimuli, and is seen even in animals with the simplest of sensory systems. In a form of non-associative learning known as nociceptive sensitization, organisms respond to harmful stimuli with defensive behaviors and maintain heightened responses even in the absence of the stimuli. While the molecular mechanisms underlying nociceptive sensitization are increasingly characterized, it is unclear how conserved they are across the animal kingdom. DNA methylation (DNAm) has been shown in different species to regulate learning and memory paradigms, including nociceptive sensitization in some instances. In this study, we hypothesize that DNAm regulates nociceptive responses in the tobacco hornworm, Manduca sexta. We have identified putative DNAm genes in the M. sexta genome, and have used a behavioral assay to determine changes in the threshold force to elicit a defensive striking behavior before and after either a strong (pinch to the body wall) or mild (injection) stimulus. Vehicle-injected animals typically remain unaffected by the injection, yet become sensitized after a pinch, where subsequent testing results in a strike threshold that is significantly lower than baseline. Injecting DNAm inhibitors, RG108 and Zebularine, not only countered the decrease in threshold typically seen in sensitized animals, but also facilitated a decrease in threshold in response to the injection. These results suggest that DNAm mediates both nociceptive responses to strong stimuli and anti-nociceptive responses to mild stimuli. Methylation and bioinformatics analyses will be done to further assess these findings and identify genes that are differentially methylated in nociceptive responses.
