Buprenorphine Rodent Analgesia

There are three types of buprenorphine.  Almost all researchers are using one of two long acting forms described below.  Extended Release (XR) Buprenorphine (Ethiqa Rx) and Sustained Release (ER) Burprenorphine.  Ethiqa may be ordered through the SMH Pharmacy.

1.  Extended Release (XR) Buprenorphine (Ethiqa XR™)

1. Dosage and Dosing Interval:

2. How to purchase: 
   1. By the vial from Pharmacy (recommended for labs performing a high volume of procedures)
      1. A 3ml vial (~$415) is sufficient to provide 72h analgesia to ~60 mice or ~20 rats.
      2. E-mail ARLControlledSubstanceOrders@urmc.rochester.edu to place an order.
      3. You must have a DEA controlled substance cabinet approved by Pharmacy and a UCAR-approved protocol describing the use of buprenorphine. 
      4. Please include the following on your POs:

• Number of vials requested
• Email address of contact person
• PI’s name
• UCAR number
• Account number to be billed
• Two signatures

5. Pick up orders at the pharmacy located in the basement just off the green elevators.
1. By dose/aliquot from DCM (recommended for labs performing infrequent/few procedures)
   1. DCM charges a dispensing fee of $16.59 per order plus the drug cost ($138/ml). Typical drug costs per dose are:
      1. Mouse: $6.90 per dose (25g BW)
      2. Rat: $20.70 per dose (300g BW)
   2. Electronically submit this REDCap form at least 2 business days in advance to the Animal Resource Office (hours: Mon-Fri 8 AM – 4:30 PM).
   3. Drug dispensed by DCM will be labeled with a 7-day expiry date.
   4. Up to 3 doses will be supplied in individual syringes by DCM. Larger orders will be aliquoted into a sterile vial and dispensed with syringes for the lab to draw up.
2. Additional notes
   1. EthiqaXR must be shaken thoroughly before each use. This drug is formulated in a viscous and sticky cholesterol-containing vehicle that may settle. A small amount of residual sediment in the vial is expected.

2.  Sustained Release (ER) Buprenorphine (“BupER” or “BupSR”)

1. In accordance with UCAR Policy and OLAW guidance regarding the use of non-pharmaceutical grade substances, this compounded product is no longer available for routine use in adult mice and rats, since an FDA-indexed product (EthiqaXR) is now on the market.
2. Exceptions may apply. Consult with a DCM veterinarian (DCMvets@urmc.rochester.edu) if you have questions or concerns.

3.  Short Acting Buprenorphine HCL

1. Dosage and Dosing Interval: 

2. How to purchase 
   1. E-mail ARLControlledSubstanceOrders@urmc.rochester.edu to place an order 
      1. A single 1-ml vial (~$12) will provide 72h of analgesia to ~1 rat or ~6 mice. 
      2. You must have a DEA controlled substance cabinet approved by Pharmacy and a UCAR-approved protocol describing the use of buprenorphine.

Tips for Subcutaneous Administration:   Use a single-use insulin syringe for each dose (provided with EthiqaXR when ordered from Animal Resource-DCM). Be aware that the long-acting suspensions are oil-based and take patience to draw up.  Mouse SQ Injection handout

Post-Operative Monitoring Documentation:  Please be certain to fully complete and insert a green post-op card, per usual practice, in each cage card holder. Even though the long-acting buprenorphine affords 48 to 72 hours of analgesia, research staff must document daily observations on the green post-op cage card and 24 hours beyond the 72-hour analgesic therapeutic range to confirm a pain-free, post-operative mouse after analgesics wear off.   

Specific Risk Factor for Respiratory Depression: First-time users of buprenorphine occasionally observe respiratory depression intra-operatively in mice or rats.  Respiratory depression poses no challenge when using inhalation isoflurane given gas anesthesia’s wide margin of safety and ease of adjustment.  However, if using injectable anesthetics (e.g. ketamine-xylazine), be aware that you may need to reduce the xylazine component of the anesthetic dose or wait several hours after pre-emptive administration before performing surgery to avoid intra-operative respiratory depression. 

The Animal Resource provides isoflurane anesthetic vaporizers free of charge for your use in most rodent procedure rooms. Research staff need to purchase their own bottle of isoflurane to use this equipment. Isoflurane vaporizers are also available to rent for a daily fee in research labs outside of the vivarium. To purchase isoflurane, submit your order here. Request training by filling out this link.

References:

1.  American College of Laboratory Animal Medicine Formulary 2024.
2. Alamaw ED, Franco BD, Jampachaisri K, Huss MK, Pacharinsak C. (2022) Extended-release Buprenorphine, an FDA-indexed Analgesic, Attenuates Mechanical Hypersensitivity in Rats (Rattus norvegicus). JAALAS 61(1): 81-88.
3. Dyson MC, Jirkof P, Lofgren J, Nunamaker EA, Pang D (Eds). Anesthesia and Analgesia in Laboratory Animals, Third Edition. (2023). Elsevier Inc.
4. Fidelis Animal Health. “Efficacy & Safety.” Ethiqa XR, 2024. https://ethiqaxr.com/efficacy-safety/
5. Foley PL, Kendall LV, Turner PV. (2019). Clinical Management of Pain in Rodents. Comp Med, 69(6), 468-489.
6. Oh SS & Narver HL. (2024). Mouse and rat anesthesia and analgesia. Current Protocols, 4, e995. doi: 10.1002/cpz1.995
7. Waite ME, Tomkovich A, Quinn TL, Schumann AP, Dewberry LS, Totsch SK, Sorge RE. (2015) Efficacy of Common Analgesics for Postsurgical Pain in Rats. JAALAS, 54(4):420-5.
8. Clark, T. S., Clark, D. D., & Hoyt, R. F. (2014). Pharmacokinetic comparison of sustained-release and standard buprenorphine in mice. Journal of the American Association for Laboratory Animal Science, 53(4), 387-391.
9. Kendall, L. V., Wegenast, D. J., Smith, B. J., Dorsey, K. M., Kang, S., Lee, N. Y., & Hess, A. M. (2016). Efficacy of sustained-release buprenorphine in an experimental laparotomy model in female mice. Journal of the American Association for Laboratory Animal Science, 55(1), 66-73.
10. Jirkof, P., Tourvieille, A., Cinelli, P., & Arras, M. (2015). Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation. Laboratory animals, 49(3), 177-187.
11. Carbone, E. T., Lindstrom, K. E., Diep, S., & Carbone, L. (2012). Duration of action of sustained-release buprenorphine in 2 strains of mice. Journal of the American Association for Laboratory Animal Science, 51(6), 815-819.
12. Healy, J. R., Tonkin, J. L., Kamarec, S. R., Saludes, M. A., Ibrahim, S. Y., Matsumoto, R. R., & Wimsatt, J. H. (2014). Evaluation of an improved sustained-release buprenorphine formulation for use in mice. American journal of veterinary research, 75(7), 619-625.
13. Adamson, T. W., Kendall, L. V., Goss, S., Grayson, K., Touma, C., Palme, R., ... & Borowsky, A. D. (2010). Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad. Journal of the American Association for Laboratory Animal Science, 49(5), 610-616.