Expression and Treatment of Pain-Related Depression of Nesting Behavior in Male ICR Mice

Abstract

Consequences of pain include pain-related functional impairment and depression of behavior, including decreased ability to work and exercise. Such pain-related depression of behavior is one of the primary treatment targets for clinicians. In contrast, most preclinical pain research with animal models has examined pain-stimulated behaviors such as reflexive withdrawal from a pain stimulus. This approach bears little resemblance to clinically-relevant pain-related behavioral depression. Moreover, reliance on this approach may have limited the development of novel, effective pharmacological pain treatments. The present studies rely on the innate nesting behavior of mice as a behavioral baseline to study the expression and treatment of pain-related depression of behavior. On test days, six pieces of cotton nesting material were evenly distributed on the homecage floor, and consolidation of this material was quantified over the course of a 100-min session. Control nesting was compared to nesting in sessions preceded by an intraperitoneal injection of dilute lactic acid (IP acid), a commonly used, physiologically-relevant noxious stimulus. When IP acid was administered prior to nesting sessions, the rate of nest consolidation was decreased. Ketoprofen, a clinically-effective non-steroidal anti-inflammatory drug (NSAID), blocked IP acid-induced depression of nesting. These findings support the utility of this assay of noxious stimulus-depressed nesting for research on the expression and treatment of pain-related depression of behavior. Future studies will use the procedure to examine the efficacy of monoamine uptake inhibitors with varying selectivity for blocking uptake of dopamine, serotonin, and norepinephrine.