Thermal sensitivity as a measure of spontaneous morphine withdrawal in mice

IntroductionOpioid withdrawal syndrome is a critical component of opioid abuse and consists of a wide array of symptoms including increases in pain sensitivity (hyperalgesia). A reliable preclinical model of hyperalgesia during opioid withdrawal is needed to evaluate possible interventions to alleviate withdrawal. The following study describes a method for assessing increases in thermal sensitivity on the hotplate in a mouse model of spontaneous morphine withdrawal.MethodsC57BL/6J mice received 5.5 days of 30, 56, or 100 mg/kg morphine or saline (s.c., twice daily). In Experiment I, thermal sensitivity data were collected at baseline and at 8, 24, 32, 48 h and 1 week following the final injection. Thermal sensitivity was assessed by examining latency to respond on a hotplate across a range of temperatures (50, 52, 54, and 56 °C). In Experiment II, 0.01 mg/kg buprenorphine was administered 30 min prior to each testing session during the withdrawal period. In Experiment III, jumping during a 30 min period was assessed at baseline and at 0, 8, 24, 32, and 48 h following the final morphine injection.ResultsDuring the withdrawal period, thermal sensitivity increased significantly in all morphine-treated mice as compared to saline-treated mice. Thermal sensitivity was greater in mice treated with 56 mg/kg morphine compared to 30 mg/kg and peaked earlier than in mice treated with 100 mg/kg (32 h v 1 wk). The increase in thermal sensitivity following 56 mg/kg morphine was attenuated by a dose of buprenorphine that did not produce antinociception alone (i.e., 0.01 mg/kg). In general, the results of the jumping experiment paralleled those obtained in Experiment I.DiscussionResponse latency on the hotplate is a reliable and sensitive measure of spontaneous morphine withdrawal in mice, making it an ideal behavior for assessing the potential of medications and environmental interventions to alleviate opioid withdrawal.