Role of Opioid Analgesic Efficacy in the Treatment of Pain-Related Disruption of Behavior in Male and Female Mice

Abstract

<b>Abstract ID 23576</b> <b>Poster Board 209</b> A key goal in preclinical pain research is improvement of the translational value of findings by modeling pain states elicited in humans. Examining the expression and treatment of pain-related disruption of behavior represents one approach to improving the alignment between preclinical pain research and clinical settings. Past studies support the ability of the opioid, analgesic morphine to restore pain-related depression of behavior in mice and rats. The goal of the present study was to examine the role of mu opioid receptor agonist efficacy in the treatment of pain-related depression of behavior. The partial mu opioid receptor agonist buprenorphine, and the full mu opioid receptor agonist methadone were examined for their ability to block lactic-acid induced depression of Nestlet shredding in male and female ICR mice. At the start of test sessions, a 5 × 5 cm Nestlet was weighed and suspended from the wire lid of the home cage. Under control conditions, mice removed pieces of the suspended Nestlet to build nests. Intraperitoneal injection of 0.18% lactic acid disrupted Nestlet shredding. Unlike morphine, buprenorphine failed to restore acid-induced depression of shredding. In contrast, methadone significantly blocked acid-induced depression of shredding. In the absence of acid, both buprenorphine and methadone significantly depressed shredding. These findings suggest that opioid effects on nestlet shredding in the presence and absence of pain stimuli require different levels of MOR efficacy. Disruption of shredding in the absence of a pain stimulus has lower efficacy requirements than treatment of pain-related depression of behavior. Support/Funding Information: NIA Grant R15AG055041