Sustained-release buprenorphine induces acute opioid tolerance in the mouse
2020
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Sustained-release buprenorphine induces acute opioid tolerance in the mouse
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2020
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Elsevier
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Abstract
Sustained-release buprenorphine is widely used in mice with the intention of providing long-lasting analgesia. Statements about duration of therapeutic efficacy are based on persistence of serum buprenorphine levels over a minimum threshold, but behavioral data demonstrating sustained efficacy is not established. Additionally, chronic opioid exposure can induce tolerance and/or hyperalgesia; mice receiving sustained-release buprenorphine have not been evaluated for these effects. This study assessed clinical efficacy and duration of sustained-release buprenorphine in inflammatory, post-operative, and cancer pain; and screened for centrally-mediated opioid-induced hyperalgesia as well as opioid tolerance. At 1-2 mg/kg sustained-release buprenorphine, statistically significant analgesic efficacy occurred only at time points up to 2 h. These animals showed no changes in von Frey thresholds on the contralateral side, i.e. no centrally-mediated opioid hyperalgesia. To establish whether acute onset opioid tolerance resulted from a single sustained-release buprenorphine administration, we used the tail flick assay, exposing mice to sustained-release buprenorphine or saline on Day 1 and buprenorphine on Day 2. We measured duration and efficacy of 1 mg/kg buprenorphine after 1 mg/kg sustained-release buprenorphine, and also quantified a dose-response curve of buprenorphine (0.1-3 mg/kg) after 2 mg/kg sustained-release buprenorphine. Compared to control animals, mice previously exposed to sustained-release buprenorphine showed diminished analgesic response to buprenorphine; the resultant dose-response curve showed decreased efficacy. Pretreatment with naloxone, an opioid receptor antagonist, blocked sustained-release buprenorphine analgesic action. The short duration of antinociception following administration of sustained-release buprenorphine in mice is caused by the rapid development of tolerance.
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10.1016/j.ejphar.2020.173330.
Previously Published Citation
Christina Larson, Cristina Peterson, Kelley Kitto, George Wilcox, Carolyn Fairbanks. 2020. Sustained-release buprenorphine induces acute opioid tolerance in the mouse. Eur J Pharmacol 2020 Oct 15;885:173330.
Suggested citation
Larson, Christina M.; Peterson, Cristina D.; Kitto, Kelley F.; Wilcox, George L.; Fairbanks, Carolyn A.. (2020). Sustained-release buprenorphine induces acute opioid tolerance in the mouse. Retrieved from the University Digital Conservancy, 10.1016/j.ejphar.2020.173330..
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