Abstract

Objective and automatic measurement of pain in mice remains a barrier for discovery in neuroscience. Here, we capture paw kinematics during pain behavior in mice with high-speed videography and automated paw tracking with machine and deep learning approaches. Our statistical software platform, PAWS (Pain Assessment at Withdrawal Speeds), uses a univariate projection of paw position over time to automatically quantify seven behavioral features that are combined into a single, univariate pain score. Automated paw tracking combined with PAWS reveals a behaviorally divergent mouse strain that displays hypersensitivity to mechanical stimuli. To demonstrate the efficacy of PAWS for detecting spinally versus centrally mediated behavioral responses, we chemogenetically activated nociceptive neurons in the amygdala, which further separated the pain-related behavioral features and the resulting pain score. Taken together, this automated pain quantification approach will increase objectivity in collecting rigorous behavioral data, and it is compatible with other neural circuit dissection tools for determining the mouse pain state.

Highlights

  • Numerous genetic and environmental factors shape the subjective experience of pain

  • The past fifty years of pain research have relied on the paw withdrawal reflex metric to measure pain-related behaviors in rodents, which has contributed to important discoveries about nociception[3, 4]

  • Beginning with six commonly used genetically inbred mouse strains we revealed stereotyped subsecond paw trajectory patterns, with simple up-down lifts typifying the response to innocuous stimuli and elaborate sinusoidal patterns typifying the responses to noxious stimuli

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Summary

Introduction

Numerous genetic and environmental factors shape the subjective experience of pain. While humans can articulate the intensity and unpleasantness of their perceived pain in the form of pain scales and questionnaires[1, 2], determining pain states in non-verbal animals remains a significant challenge. Rodents are the predominant model organism to study pain and there is an urgent need to develop high-throughput approaches that accurately measure pain. The past fifty years of pain research have relied on the paw withdrawal reflex metric to measure pain-related behaviors in rodents, which has contributed to important discoveries about nociception[3, 4]. The traditional approach of manually scoring paw lifting suffers from an inability to determine whether paw movement away from a stimulus is motivated by the experience of pain. Increasing the dimensionality, of the common paw withdrawal assay has the potential to increase the predictive validity of translational pain therapeutics, and to increase the rate at which basic science findings are translated to the clinic

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