It is well established that appropriate responses to pain are essential for the survival of all animals, but there are inherent difficulties in carrying out studies aimed at understanding the biology of pain. Pain research in humans is practically difficult, inherently subjective, and ethically constrained. Pain research in non-human animals is problematic because animals cannot rank and communicate their pain consciously and thus, especially when using invertebrate models, one must infer the pain level from high precision experiments that characterize animal behavior. Such analyses are typically qualitative and not necessarily reflective of the complex and multidimensional nature of pain behavioral responses. This project will solve the multidimensional data analysis and behavioral modeling problem using modern information-theoretic tools. The roundworm, C. elegans, will serve as the model organism for pain studies since it is genetically tractable and offers opportunities for high-throughput, quantitative, behavioral characterization. Worm behavioral data will be collected in response to nociceptive stimuli using a custom tracking microscope. Data will be fitted to a computational model that will allow reconstruction of the applied pain level as predicted from the behavioral output. The model will filter out confounding effects of the worm's physiological state. The project will explore reliability and robustness of the pain response, and it will identify neuronal mediators of the response. This will be the first comprehensive characterization of stimulus induced whole-organism behavior in eukaryotic organisms and will build on pioneering work carried out on bacterial chemotaxis. The project is expected to impact biomedical research by enabling objective characterization of pain transduction in animal models. It will impact the scientific community by promoting research and education on quantitative, computational characterization of sensory induced behaviors using topical workshops. It will further impact STEM training in high schools and colleges by developing new classes, modules, and curricula related to quantitative studies of behavior, and, more generally, to quantitative biology.
