Preclinical postoperative pain trajectories: impact of experimental predictors on recovery

This study examined the contribution of experimental predictors to aspects of postoperative pain trajectories in rats following surgery. We conducted Linear Mixed Effects (LME) growth curve modeling of longitudinal mechanical paw withdrawal thresholds (PWTs) in 164 Sprague Dawley rats from 7 independent cohorts that underwent partial L5 spinal nerve ligation. The dependent variable of LME was the PWTs response value in log-transformed form and the fixed effects included baseline PWTs, interested internal factors and linear time as a continuous variable, while setting subject IDs as random intercepts and linear time as random slopes. Mechanical PWTs increased over 10 weeks in a curvilinear fashion for the entire group of rats with significant inter-individual variability in intercept or initial hypersensitivity and slope of recovery. We examined the influence of several internal experimental predictors including surgeon, preoperative stress exposure, daily running wheel exposure, age at time of surgery and housing facility to model fit and trajectory parameters using both univariate and multivariate LME models. We found that surgeon (p