Mapping the neuroethological signatures of pain, analgesia and recovery in mice (Q6725209)

Mapping the neuroethological signatures of pain, analgesia and recovery in mice. Repository containing datasets obtained for M. Bohic, L Pattison, etal. 2023. Neuron. Abstract Ongoing pain is driven by direct activation of pain-sensing neurons and neuroimmune mediatedsensitization. These heightened pain states alter physiology, reduce motor function, and affect motivationto engage in normal behaviors. The complexity of the pain state has evaded a comprehensive definition,especially in nonverbal animals. Here in mice, we capture the physiological state of sensitized neuronsand use computational tools to automatically map behavioral signatures of evoked and spontaneousdisplays of pain at different time points for both an acute model of paw inflammatory pain and a chronicmodel of knee joint pain. First, retrograde labeling coupled with electrophysiology of neurons innervatinginjury sites revealed key time points corresponding to peripheral sensitivity in multiple pain models. Next,we used high-speed videography combined with supervised and unsupervised machine learning tools touncover sensory-evoked defensive coping postures, unique to each pain condition. Using 3D poseanalytics inspired by natural language processing, we identify movement sequences that correspond torobust representations of ongoing pain states. With this new analytical framework, we find that commonlyused analgesics do not return an animals behavior to a pre-injury state. Instead, animals adopt a novelset of spontaneous behaviors that are maintained even after most evoked behavioral features of painhave resolved. Together, these findings reveal previously unidentified neuroethological signatures of painand analgesia at timescales when inflammation induces heightened pain states and during recovery.