Department of Biology
University of Pennsylvania
A Mouse Pain Scale: Assessment of Pain Sensation in Mice Using Sub-second Behavioral Mapping and Statistical Modeling
Rodents are the main model systems for pain research, but determining their pain state is very challenging. To improve upon the use of the paw withdrawal reflex to objectively assess pain sensation in mice, we developed a “behavior-centered” approach that integrates multiple parameters of the withdrawal behavior, which were precisely measured with high-speed videography, into a single index via statistical modeling and machine learning.
We first verified through in vivo calcium imaging in the dorsal root ganglion of whole animals, the quality (noxious or innocuous) of the natural mechanical stimuli we used in the study. We then performed detailed analyses of sub-second mouse responses to identify behavioral features that differentiate between innocuous and noxious mechanical stimulation. With statistical modeling and machine learning techniques, we integrated these features onto a graded index, which could indicate “pain severity” or the probability a particular withdrawal was “pain-like” on a single trial basis. In contrast to the withdrawal frequency, this score correlates very well with stimulus intensity. Finally, we performed two proof-of-principle experiments to test the utility of our new methodology: one with a natural stimulus, von Frey hairs (VFHs), and the other with transdermal optogenetic stimulation of two transgenic lines that target almost all nociceptors (TRPV1-ChR2) or a smaller population of C-fiber nociceptors (MRGPRD-ChR2). Under all scenarios, our platform reliably indicates the sensation experienced by the mouse, highlighting the precision of our approach.
We strongly believe this “pain scale” method will greatly improve rigor and reproducibility of using mice as a model system to study pain mechanisms or perform drug screening, and may potentially change how the pain research field will perform, analyze, and interpret rodent reflexive behavioral assays in the future.
A pizza lunch will be served at 11:45am. The seminar will begin at 12:00pm.