Tags

Type your tag names separated by a space and hit enter

Effects of oxycodone and diazepam alone and in combination on operant nociception.

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.

Authors+Show Affiliations

Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31972623

Citation

Leonard, Michael Z., and Brian D. Kangas. "Effects of Oxycodone and Diazepam Alone and in Combination On Operant Nociception." Behavioural Pharmacology, 2020.
Leonard MZ, Kangas BD. Effects of oxycodone and diazepam alone and in combination on operant nociception. Behav Pharmacol. 2020.
Leonard, M. Z., & Kangas, B. D. (2020). Effects of oxycodone and diazepam alone and in combination on operant nociception. Behavioural Pharmacology, doi:10.1097/FBP.0000000000000542.
Leonard MZ, Kangas BD. Effects of Oxycodone and Diazepam Alone and in Combination On Operant Nociception. Behav Pharmacol. 2020 Jan 15; PubMed PMID: 31972623.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of oxycodone and diazepam alone and in combination on operant nociception. AU - Leonard,Michael Z, AU - Kangas,Brian D, Y1 - 2020/01/15/ PY - 2020/1/24/entrez PY - 2020/1/24/pubmed PY - 2020/1/24/medline JF - Behavioural pharmacology JO - Behav Pharmacol N2 - 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. SN - 1473-5849 UR - https://www.unboundmedicine.com/medline/citation/31972623/Effects_of_oxycodone_and_diazepam_alone_and_in_combination_on_operant_nociception L2 - http://dx.doi.org/10.1097/FBP.0000000000000542 DB - PRIME DP - Unbound Medicine ER -