Early Changes in Respiration and Motor Activity after Spinal Cord Injury Predict Pain-Related Outcomes in Mice

Abstract

Spinal cord injuries (SCIs) may lead to the emergence of chronic pain many weeks after injury. Using the thoracic contusion model of SCI-induced neuropathic pain, we investigated whether early changes in mouse respiration or motor activity could predict and differentiate emergent dysfunction with focus on pain. We measured respiratory rate (RR) and movement (motor activity) in freely behaving mice before and at several time points following SCI. We then assessed behavioral signs of pain or thermal dysregulation by testing evoked hindpaw withdrawal responses to mechanical and thermal heating stimuli and temperature preferences at four weeks after injury. For 2-3 days after injury, mice exhibited sharp decreases in movement and RR variability, but these two parameters were uncorrelated within animals. Mice showed signs of mechanical and thermal hypersensitivity and preferences for warmer temperatures four weeks after injury. Interestingly, mice that moved the least 1 day after SCI preferentially underwent hindpaw mechano-sensitivity (r = 0.67, p =.036), whereas mice with large decreases in RR variability that recovered by 8 days post-injury preferred higher temperatures in the thermal preference test (r = 0.79, p =.007). Thus, early changes in movement and RR variability may differentially predict future hypersensitivity and thermal dysfunction. More broadly, early post-injury physio-behavioral events could inform novel interventions to mitigate subsequent emergent dysfunction after SCI.