Data from: Ethological profiling defines pain behaviors and parses analgesia from drug side effects in a mouse model of complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a form of chronic post-injury
pain affecting the extremities with contributions from the somatic and
sympathetic nervous systems. The mouse tibial fracture-cast model was
developed to enable preclinical study of CRPS mechanisms and guide
condition-specific drug development. Given the inherent limitations of
reflex pain measures in mice, we sought to holistically characterize
pain-like behaviors in this model in neutral and aversive environments
using quantitative behavior analysis with LabGym, a user-friendly
automation tool that requires no special equipment or extensive
computational resources. Here, we show that tibial fracture-cast injury
causes distinct changes in naturalistic and nocifensive behaviors in male
and female mice in neutral and aversive environments, demonstrating
reliable behavioral categorization using robust learning-based holistic
assessment. As proof-of-concept for therapeutic testing, we leveraged this
behavioral evaluation to characterize the peripheral versus central
effects of targeting alpha-2 receptors (α2-AR) with dexmedetomidine (DEX),
a selective α2-AR agonist with analgesic, sedative and anxiolytic
properties.  We found that DEX reduced mechanical allodynia
primarily via central α2-ARs. DEX also decreased motion metrics, grooming
and rearing in an open field, and distinctly affected the quality and
quantity of grooming in an aversive environment, and systemic α2-AR
antagonists did not suppress this effect. Importantly, we also determined
that the sedative effects of DEX were attenuated in injured compared to
uninjured mice, consistent with known sympathetic nervous system
activation in CRPS.  Overall, this study highlights the use of
automated behavioral testing to parse analgesia from sedation in a unique
preclinical pain model.