Short ReportsEffects of oxycodone and diazepam alone and in combination on operant nociceptionLeonard, Michael Z.; Kangas, Brian D. Author Information Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA Received 19 November 2019 Accepted as revised 10 December 2019 Correspondence to Brian D. Kangas, PhD, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA, E-mail: [email protected] Behavioural Pharmacology: April 2020 - Volume 31 - Issue 2&3 - p 168-173 doi: 10.1097/FBP.0000000000000542 Buy Metrics Abstract Developing effective analgesics with fewer unwanted side effects is a pressing concern. Due to a lack of effective nonopioid options currently available, an alternative approach termed opioid-sparing evaluates the ability of a coadministered drug to reduce the amount of opioid needed to produce an antinociceptive effect. Opioids and benzodiazepines are often coprescribed. Although this approach is theoretically rational given the prevalent comorbidity of chronic pain and anxiety, it also has inherent risks of respiratory depression, which is likely responsible for the substantial percentage of fatal opioid overdoses that have involved benzodiazepines. Moreover, there have been no clinical trials to support the effectiveness of this drug combination nor has there been corroborative preclinical evidence using traditional animal models of nociception. The present studies examined the prescription µ-opioid analgesic oxycodone (0.003–0.1 mg/kg) and the prototypical benzodiazepine anxiolytic diazepam (0.03–1.0 mg/kg), alone and in combination, using an animal model of pain that examines the restoration of conflict-related operant behavior as evidence of analgesia. Results documented significant dose-related increases in thermal threshold following oxycodone treatment. Diazepam treatment alone did not produce significant antinociception. In combination, diazepam pretreatment shifted oxycodone functions upward in a dose-dependent manner, but the additive effects were limited to a narrow dose range. In addition, combinations of diazepam and oxycodone at higher doses abolished responding. Taken together, though intriguing, these findings do not provide sufficient evidence that coadministration of an anxiolytic will result in clinically relevant opioid-sparing for pain management, especially when considering the inherent risks of this drug class combination. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.