Expression and Treatment of Pain-Depressed Climbing in Male and Female Mice

This study evaluated climbing behavior by mice as a potential endpoint for preclinical studies on expression and treatment pain-depressed behavior. Climbing by adult male and female ICR mice was evaluated in plexiglass cylinders (11.25 cm diameter x 25.5 cm height) equipped with 0.5 cm2 wire mesh covering the inner walls. Climbing was quantified as total seconds with all four paws off the cylinder floor and at least one paw on the mesh during each 10-min behavioral session. A sequence of four experiments was conducted in separate groups of at least 12 mice (6 male, 6 female) for each experiment. Experiment 1 evaluated stability of climbing in the absence of any treatment over five test sessions conducted on Tuesdays and Fridays over a 2-week period. Experiment 2 evaluated depression of climbing by an acute, visceral noxious stimulus [intraperitoneal lactic acid (IP acid), 0-0.56% in sterile water, 10-min pretreatment time]. Experiments 3 and 4 compared effectiveness of a positive-control analgesic (the cyclooxygenase inhibitor ketoprofen, 10 mg/kg) and a negative-control non-analgesic (the centrally acting kappa opioid receptor agonist U69593, 0.1-1.0 mg/kg) to block 0.32% IP acid-induced climbing depression. For Experiments 2-4, treatments were counterbalanced across mice using a Latin-square design. Data were analyzed by one- or two-way ANOVA, and a significant ANOVA was followed by a Dunnett or Holm-Sidak post hoc test. The criterion for significance was p<0.05. Climbing was stable during within-subject, repeated testing and averaged 262±21 sec during each 10-min session (Experiment 1). IP acid produced a concentration-dependent decrease in climbing (Experiment 2) that was blocked by ketoprofen (Experiment 3) but not by U69593 (Experiment 4). These results support utility of climbing by mice as a behavioral endpoint for studies of pain-depressed behavior and for evaluation of candidate analgesics. Grant support from NIH P30DA033934, NIH R25GM090084, and NIH T32DA007027.