Animal Health & Veterinary Information

Non-Steroidal And Opioid Analgesics

In the links below you will find tables of commonly used analgesics and their dosages for Rodents, Rabbits, and Large Animals used in research. There are also recommendations, guidelines, and information on various topics relating to the overall health and well-being of research animals below.

If there are any questions, please consult with one of our health care staff and our DLAR veterinarians should you require assistance.

Analgesic	Class of Drug	Mouse	Rat	Guinea Pig	Gerbil	Hamster	Rabbit
Acetaminophen	NSAID	300 mg/kg PO	100-300 mg/kg PO (6 mg/ml drinking water)	------	100-300 mg/kg PO (6 mg/ml drinking water)	100-300 mg/kg PO (6 mg/ml drinking water)	1 ml drug/100ml drinking water
Carprofen	NSAID	10.0 mg/kg SC or PO q 12-24 hours	5-7 mg/kg SC or PO q 12-24 hours	2.5 mg/kg SC q 24 hours	5.0-10.0 mg/kg SC or PO q 12-24 hours	5.0-10.0 mg/kg SC or PO q 12-24 hours	1.5-5 mg/kg PO, or 4 mg/kg SC q 24 hours
Flunixin	NSAID	2.5 mg/kg SC q 12 hours	1.1-2.5 mg/kg SC q 2 hours	1.1-2.5 mg/kg SC q 2 hours	1.1-2.5 mg/kg SC q 2 hours	1.1-2.5 mg/kg SC q 2 hours	1.1 mg/kg SC or IM q 12 hours
Ketoprofen	NSAID	------	5.0 mg/kg IM q 12-24 hours	------	5.0 mg/kg IM q 12-24 hours	5.0 mg/kg IM q 12-24 hours	3.0 mg/kg IM q 24 hours
Meloxicam	NSAID	2-5 mg/kg IP q 12-24 hours	1-4 mg/kg SC or IP q 24 hours	1-2 mg/kg SC or PO q 24 hours	1.0 mg/kg SC or PO q 24 hours	1.0 mg/kg SC or PO q 24 hours	0.3-0.6 mg/kg SC or PO q 24 hours
Buprenorphine	Opioid	0.05-0.1 mg/kg SC q 3-5 hours **see below	0.01-0.05 mg/kg SC q 6-8 hours **see below	0.05 mg/kg SC q 6-12 hours	0.1-0.2 mg/kg SC q 6-12 hours	0.05-0.5 mg/kg SC q 6-12 hours	0.02-0.1 mg/kg IV or SC q 6-12 hours
Buprenorphine ER-LAB (Formerly SR-LAB)***	Opioid	1.0-1.5 mg/kg SQ Inj	0.5-1.0 mg/kg SQ Inj	------	------	------	------
Oral Buprenophine in Nutella	Opioid	See Oral Buprenophine in Nutella below for Formulation and Preparation instructions for administration to rats and mice.		------	------	------	------
Oral Buprenophine in ClearH2O Medigel Sucralose and Hazelnut flavor Medigel	Opioid	See ClearH2O Medigel Sucralose and Hazelnut flavor Medigel below for Formulation and Preparation instructions for administration to rats and mice.		------	------	------	------
Nalbuphine	Opioid	4-8 mg/kg IM q 4 hours	2-5 mg/kg IM q 4 hours	1-2 mg/kg IM q 4 hours	1-2 mg/kg IM q 4 hours	1-2 mg/kg IM q 4 hours	1-2 mg/kg IM or IV q 4 hours
Meperidine (Demerol)	Opioid	10-20 mg/kg SC or IM q 2-3 hours	10-20 mg/kg SC or IM q 2-3 hours	10-20 mg/kg SC or IM q 2-3 hours	10-20 mg/kg SC or IM q 2-3 hours	10-20 mg/kg SC or IM q 2-3 hours	5-10 mg/kg SC or IM q 2-3 hours

Other analgesics and multimodal combinations of analgesics can be used. Please consult with a DLAR veterinarian for further details.
** Contact our DLAR Veterinarians for further information if needed
*** Dose depending on pain severity: DLAR recommends that you access more information below on the Proper Dosing of Buprenorphine SR-Lab and Buprenorephine SR-LAB Administration Instructions.

DLAR also recommends giving Injectable analgesic during surgery or at the beginning of surgery to allow time for the analgesic to begin working before the animal would be perceiving pain. Preferably allow 30 minutes to one hour.

References:

Anesthesia and Analgesia in Laboratory Animals, Second Edition, Richard E Fish, Marilyn J Brown, Peggy J Danneman, Alicia Z Karas (eds.) American College of Laboratory Animal Medicine Series, 2008.
Formulary for Laboratory Animals, Third Edition, Compiled by C Terrance Hawk, Steven L Leary, Timothy H Morris, American College of Laboratory Animal Medicine and European College of Laboratory Animal Medicine, Blackwell Publishing, 2005.
Formulary for Laboratory Animals, Second Edition, Compiled by C Terrance Hawk, Steven L Leary, Timothy H Morris, American College of Laboratory Animal Medicine and European College of Laboratory Animal Medicine, Blackwell Publishing, 1999.
ZooPharm Formulation for: Pain Management in Laboratory Animals Information Sheet Buprenophine SR™ Lab

Analgesic	Class of Drug	Ferret	Cat	Dog	Pig	Sheep	NHP
Carprofen	NSAID	2-4 mg/kg PO or SC q 24hrs	4.0 mg/kg SC or IV once only	2.0 mg/kg SC or IV q12 hrs or 4.0 mg/kg SC or IV q24 hrs.	2.0-4.0 mg/kg SC or IV q 24h for 2-3 days	1.5-2.0 mg/kg SC or IV q 24h for 2-3 days	2.0-4.0 mg/kg SC or PO q 24 hrs up to 4 days
Flunixin	NSAID	0.3 mg/kg PO or SC q 24hrs	1.0 mg/kg IV or IM q 24 hrs	1.0 mg/kg IV or IM q 24 hrs	1.0-2.2 mg/kg IV or SC q 24 hrs	1.5-2.0 mg/kg IV or SC q 24 hrs	2.0-4.0 mg/kg SC or IV q 24 hrs
Ketoprofen	NSAID	1-2 mg/kg PO or SC q 24hrs	2.0 mg/kg SC q 24 hrs up to 3 days	2.0 mg/kg SC q 24 hrs up to 3 days	3.0 mg/kg SC only once	1.0 mg/kg IM q 24hrs for up to 3 days	------
Meloxicam	NSAID	0.2 mg/kg PO or SC q 24hrs	0.2 mg/kg SC or PO on first day of treatment, then 0.1 mg/kg q 24 hrs	0.2 mg/kg PO or SC q 24hrs	0.2-0.3 mg/kg SC or PO q 24 hrs	------	0.2-0.3 mg/kg PO q 24 hrs up to 4 days
Buprenorphine	Opioid	0.01-0.03 mg/kg IM, SC, or IV q 8-12 hrs	0.005-0.01 mg/kg IM, SC, or IV q 8-12 hrs	0.005-0.02 mg/kg IM, SC, or IV q 6-12 hrs	0.005-0.02 mg/kg IM, SC, or IV q 6-12 hrs	0.005-0.01 mg/kg IM, SC, or IV q 6-12 hrs	0.01-0.02 mg/kg IM, or SC q 6-12 hrs
Butorphanol	Opioid	0.2-0.8 mg/kg IM or SC q 2 hrs	0.2-0.4 mg/kg IM, or IV q 3-4 hrs	0.2-0.4 mg/kg IM, or IV q 3-4 hrs	0.1-0.3 mg/kg IM q 4-6 hrs	0.5 mg/kg SC q 2-3 hrs	0.05 mg/kg IM q 6-8 hrs
Morphine	Opioid	0.5-2 mg/kg IM or SC q 4-6 hrs	0.1 mg/kg IM q 4 hrs	0.5-5.0 mg/kg IM q 4 hrs	0.2-1.0 mg/kg IM q 4 hrs	0.1-2.0 mg/kg IM q 4 hrs	0.2-1.0 mg/kg IM q 4 hrs
Pethidine (Meperidine)	Opioid	5-10 mg/kg IM q 2-4 hrs	2-10 mg/kg IM or IV q 2 hrs	6-10 mg/kg IM or SC q 2-3 hrs	2 mg/kg IV q 4 hrs OR 4-10 mg/kg IM	2 mg/kg IM q 2 hrs	2-4 mg/kg IM q 4 hrs
Fentanyl	Opioid	------	Patch q 72hrs	Patch q 72hrs	IV q 4 hrs	------	------

Other analgesics and multimodal combinations of analgesics can be used. Please consult with a DLAR veterinarian for further details.

References:

Anesthesia and Analgesia in Laboratory Animals, Second Edition, Richard E Fish, Marilyn J Brown, Peggy J Danneman, Alicia Z Karas (eds.) American College of Laboratory Animal Medicine Series, 2008.
Formulary for Laboratory Animals, Third Edition, Compiled by C Terrance Hawk, Steven L Leary, Timothy H Morris, American College of Laboratory Animal Medicine and European College of Laboratory Animal Medicine, Blackwell Publishing, 2005.
Formulary for Laboratory Animals, Second Edition, Compiled by C Terrance Hawk, Steven L Leary, Timothy H Morris, American College of Laboratory Animal Medicine and European College of Laboratory Animal Medicine, Blackwell Publishing, 1999.

Preparation and Dosing Guides

An investigator at UK has been using buprenorphine/Nutella for several years, now, in mice and rats. You need 2 mg sublingual buprenorphine tablets (Subutex or Temgesic NOT Suboxone). The proportions of the mixture are 2 g Nutella per kg bw animal and 0.4 mg/kg bw buprenorphine.

For the rats, crush the 2 mg tablet and add it to 10 g Nutella (final concentration 0.2mg/g), and it dissolves pretty well. This is too concentrated for the mice, so add the buprenorphine to twice the amount of Nutella, 20 g (final concentration 0.1mg/g).

For example, for a 30 g mouse:

0.4 mg/kg x 0.03 kg divided by 0.1 mg/g = 0.12 g or 120 mg of mixture.

The Buprenorphine/Nutella mixture is supposed to be given 1 hour before the surgery or procedure that you are doing, and again 12-24 hours later. You can acclimate the mice to the Nutella without drug by smearing it on the side of their cage. They usually love it, but, you have to get them used to it so that they eat it right away. It usually takes 3-4 days. If mice are singly housed , this makes it easy in assuring that the right mouse gets the drug.

An Investigator experienced with this method of analgesia has stated that this method of buprenorphine delivery is good for maintaining pain control, but, not enough for initial moderate to severe pain. You may want to give a SC injection of buprenorphine at the time of surgery along with several days of oral buprenorphine every 12-24 hrs.

Note: If the USP tablets are not available there is a Sigma product, B9275, Buprenorphine Hydrochloride Powder of ~97% purity. You will need to justify non pharmaceutical grade in your IACUC protocol or amendment.

References:

Gades, NM, Danneman, PJ, et al. 2000. The Magnitude and Duration of the Analgesic Effect of Morphine, Butorphanol, and Buprenorphine in Rats and Mice. Contemporary Topics 39-2:8-13
Foley PL, Liang H, and Crichlow AR. 2011. Evaluation of a Sustained-Release Formulation of Buprenorphine for Analgesia in Rats. Journal AALAS. 50(2):198-204
Kalliokoski O., Jacobsen KR., et al. 2011. Serum Concentrations of Buprenorphine after Oral and Parenteral Administration in Male Mice. The Veterinary Journal 187:251-254.
Wala EP, and Holtman JR. 2011. Buprenorphine-induced Hyperalgesia in the Rat. European Journal of Pharmacology 651:89-95
Curtin LI,Grakowsky JA, et al. 2009. Evaluation of Buprenorphine in a Postoperative Pain Model in Rats. Comparative Medicine 59(1):60-71.
Blaha MD and Leon LR. 2008. Effects of Indomethacin and Buprenorphine Analgesia on the Postoperative Recovery of Mice. Journal AALAS. 47(4):8-19
Matsumiya LC, Sorge RE, et al. 2012. Using the Mouse Grimace Scale to reevaluate the efficacy of postoperative analgesics in laboratory mice. Journal AALAS. 51(1):42-49
Sotocinal SG, Sorge RE, et al. 2011 The Rat Grimace Scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions. Mol. Pain. 29(7):55.
Efficacy Studies of Diet Delivered Analgesics. Clear H20 and Bilsky Laboratory, University of New England. ClearH20 Efficacy Studies of Diet Delivered Analgesics presentation (pdf, 10pgs)

This is administered orally for mice or rats for consistent analgesia. You can make this up as you need it with your own buprenorphine injectable. This will become the animal’s sole source of water, so you will need to remove the water bottle from the cage. Each medigel is good for 24-48 hours. As the above method, this method of buprenorphine delivery is good for maintaining pain control, but, not enough for initial moderate to severe pain. You may want to give a SC injection of buprenorphine at the time of surgery along with several days of oral buprenorphine. There is a video available as well as a powerpoint presentation you may request if you are considering this method of extended analgesia administration. The video details preparation.

References:

Gades, NM, Danneman, PJ, et al. 2000. The Magnitude and Duration of the Analgesic Effect of Morphine, Butorphanol, and Buprenorphine in Rats and Mice. Contemporary Topics 39-2:8-13
Foley PL, Liang H, and Crichlow AR. 2011. Evaluation of a Sustained-Release Formulation of Buprenorphine for Analgesia in Rats. Journal AALAS. 50(2):198-204
Kalliokoski O., Jacobsen KR., et al. 2011. Serum Concentrations of Buprenorphine after Oral and Parenteral Administration in Male Mice. The Veterinary Journal 187:251-254.
Wala EP, and Holtman JR. 2011. Buprenorphine-induced Hyperalgesia in the Rat. European Journal of Pharmacology 651:89-95
Curtin LI,Grakowsky JA, et al. 2009. Evaluation of Buprenorphine in a Postoperative Pain Model in Rats. Comparative Medicine 59(1):60-71.
Blaha MD and Leon LR. 2008. Effects of Indomethacin and Buprenorphine Analgesia on the Postoperative Recovery of Mice. Journal AALAS. 47(4):8-19
Matsumiya LC, Sorge RE, et al. 2012. Using the Mouse Grimace Scale to reevaluate the efficacy of postoperative analgesics in laboratory mice. Journal AALAS. 51(1):42-49
Sotocinal SG, Sorge RE, et al. 2011 The Rat Grimace Scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions. Mol. Pain. 29(7):55.
Efficacy Studies of Diet Delivered Analgesics. Clear H20 and Bilsky Laboratory, University of New England. ClearH20 Efficacy Studies of Diet Delivered Analgesics presentation (pdf, 10pgs)

The common practice of providing analgesia to rodents experiencing severe to moderate pain (as may be seen following laminectomy or other major surgery) with parenteral (IV, SC, IM) buprenorphine every 12 hours is not supported by the literature. Pharmacokinetic and behavioral observations indicate a much shorter effective period with redosing required at 3-5 hours in mice and 6-8 hours in rats. There are new alternative formulations of buprenorphine for extended provision of analgesia. The options include orally administered analgesia recipes you may make which provide 12-24 hours of analgesia and a sustained release injectable product which provides up to 72 hours of analgesia. Please contact DLAR Veterinary Staff for specifics and to design an analgesia protocol that is best for your research and the animal’s well-being.

Buprenorphine SR-LAB Administration Instructions

Buprenorphine SR-LAB does not need to be stored refrigerated. The 1 mg/ml Buprenorphine SR-LAB formulation will retain stability even without refrigeration. This formulation has been tested at room temperature for one year and has retained its stability and efficacy, while this is not true for the Buprenorphine SR-HCl formulated for other species where this formulation must be refrigerated to maintain stability and efficacy. However, the drug is viscous and more difficult to inject when cold. Prior to use the preparation should be warmed to room/ body temperature. The drug is hygroscopic (draws in moisture that causes polymerization). It should not be drawn into syringes and stored for periods of time as moisture in the air has been reported to result in precipitation and polymerization.

Due to its viscosity an 18-gauge needle should be used to draw-up Buprenorphine SR-LAB from its stock vial. A 1cc, Luer-lock type syringe is recommended to reduce the chance of syringe-needle hub leak/separation as a good “push” is required for injection.

To minimize the chance of reaction precise subcutaneous injection using the a 21 or 25-gauge needle should be used to reduce backflow from the injection track is recommended. The skin puncture site should also be gently pinched for 10 seconds following injection to assist sealing. Intradermal (ulceration) or injection into muscle tissue (increased blood levels) must be avoided. NOTE, there have been reports of skin irritation with prior formulations of Buprenorphine SR that has been rectified with the Buprenorphine SR-LAB formulation.

DLAR Veterinary Staff recommends Buprenorphine SR-LAB (1mg/ml) should be administered at the beginning of surgery. Anesthesia facilitates precise subcutaneous injection and allows time for the drug to reach therapeutic blood levels (30 min to one hour) before the animal would be perceiving pain.

Please contact the DLAR Veterinary Staff for further information and assistance with use of this product or additional questions.

Calculate Dosage by noting a dosage of normal Buprenorphine == (#) mg/kg X number of doses that would be given in 72 hours (for 3-day duration).

MOUSE DOSE 0.72 mg/kg to 1.44mg/kg Buprenorphine SR-Lab given once every 3 days (dose depending on pain severity).

*** i.e. for mouse given 0.05mg/kg q 5 hours=0.05mg/kg X 14.4=0.72 mg/kg of Buprenorphine SR Lab given by subcutaneous injection or for mouse given 0.1 mg/kg q 5 hours =0.1mg/kg X 14.4=1.44 mg/kg of Buprenorphine SR-Lab given by subcutaneous injection.

RAT DOSE 0.6 mg/kg Buprenorphine SR-Lab given once every 3 days

*** i.e. for rat given 0.05 mg/kg q 6 hours for 72 hours==0.05 mg/kg X 12==0.6 mg/kg of Buprenorphine SR-Lab given by subcutaneous injection. Based on the observation of pica behavior in some rats dosed at 1.2 mg/kg, the DLAR Veterinary Staff recommendations is to begin with a 0.6 mg/kg dose for initial treatment.

However, if indications of pain or distress are observed DLAR veterinarians should be contacted to evaluate the animal(s) and modify the analgesic dose/plan as needed.