The Animal Research Committee (ARC) is requesting comments on a proposed revision to post-operative buprenorphine dosing in mice and rats. The proposal reflects evidence regarding analgesic duration, promotes the use of extended-release formulations where appropriate, and introduces revised dosing schedules intended to improve pain management and animal welfare.
Please closely read the below proposal. Comments must be submitted to arc@research.ucla.edu by close of business on Wednesday, November 4, 2026. The ARC will be informed of all submitted comments when making final recommendations.
–PROPOSED REVISION OF BUPRENORPHINE HCL DOSING FOR POST-OPERATIVE ANALGESIA IN RODENTS–
Background
The UCLA Animal Research Committee (ARC) reviewed recent literature regarding the effectiveness of standard buprenorphine hydrochloride (Buprenorphine HCl) for post-operative pain management in rodents. Current ARC requirements generally permit dosing every 8 to 12 hours. However, a growing body of pharmacokinetic and efficacy data indicates that this interval does not consistently provide continuous analgesia in mice and rats. Evidence suggests that therapeutic plasma concentrations and measurable analgesic effects frequently decline well before the next scheduled dose, creating gaps in pain control.
Proposed actions
1. Preferential Use of Extended-Release Buprenorphine
When post-operative opioid analgesia is indicated, investigators will be encouraged to use extended-release (ER) buprenorphine formulations whenever scientifically appropriate.
ER products provide more consistent analgesic coverage while reducing handling and frequency of injections. Studies have demonstrated that extended-release formulations can maintain therapeutic plasma concentrations for 48 to 72 hours following a single administration (see citations below).
2. Revised Dosing Schedule for Standard Buprenorphine HCl
When ER formulations cannot be used, Buprenorphine HCl (0.1-0.5 mg/kg for mice; 0.05-0.1 mg/kg for rats) must be administered at increased frequency based on the analgesic regimen employed as follows:
As part of a multimodal analgesic plan (e.g., combined with an NSAID or local anesthetic):
- Mice and rats: every 6 to 8 hours
When used as the sole analgesic:
- Mice: every 4 to 6 hours
- Rats: every 6 to 8 hours
These recommendations are supported by both pharmacokinetic and efficacy studies. Foley and colleagues’ comprehensive review of rodent pain management found that plasma concentrations above the commonly accepted therapeutic threshold are rarely maintained after administration of standard buprenorphine beyond approximately 4 to 6 hours in mice and 6-8 hours in rats. Multiple efficacy studies summarized in the review further demonstrated that the analgesic effects of standard buprenorphine frequently diminish within 4 to 8 hours following administration, whereas sustained-release formulations maintain analgesic benefit for 24 to 72 hours.
3. Implementation
Investigators using Buprenorphine HCl for post-operative analgesia will be required to update affected protocols either:
- At the time of the next non-administrative amendment, or
- Within one year of the ARC announcement,
whichever occurs first.
The ARC will prepare new Buprenorphine HCl standard procedures with the increased dosing frequency for investigator use.
Protocol amendments limited to implementation of the revised dosing schedule may be reviewed through the Chair/Veterinarian process provided no additional changes requiring Designated Member Review (DMR) or Full Committee Review (FCR) are included.
Key References
- Foley PL, Kendall LV, Turner PV. Clinical Management of Pain in Rodents. Comparative Medicine. 2019;69(6):468-489.
- Huss MK, Pacharinsak C. A Review of Long-acting Parenteral Analgesics for Mice and Rats. Journal of the American Association for Laboratory Animal Science. 2022.
- Saenz M, Bloom-Saldana E, Synold T, et al. Pharmacokinetics of Sustained-release and Extended-release Buprenorphine in Mice after Surgical Catheterization. JAALAS. 2022.
- Alamaw ED, Franco BD, Jampachaisri K, et al. Extended-release Buprenorphine Attenuates Mechanical Hypersensitivity in Rats. JAALAS. 2022.