Alternatives to Acetaminophen for Pain Control Methods in Rats and Mice
Acetaminophen (Tylenol) has long been used by RAR for easily administered pain relief through the drinking water for rats and mice. However, this drug has not been proven to be an effective pain reliever when administered in this manner. Using acetaminophen in the drinking water for pain relief in rodents does not meet current best practices and is not currently acceptable.
| Current Recommendations for Analgesia in Rats and Mice | ||||
|---|---|---|---|---|
| Drug Name* | Species | Dose | Frequency | Controlled Substance? |
| Aspirin | Rodents | 100-400 mg/kg | 1-2X per day | No |
| Meloxicam | Rats | 1.0 mg/kg | Daily | No |
| Buphrenorphine | Rodents | 0.01-0.02 mg/ml drinking water | Daily | Yes |
| Buphrenorphine | Rodents | 0.5 mg/kg in jello | Daily | Yes |
| Carprofen | Rodents | 5-10 mg/kg in water or jello | Daily or once post-operatively | No |
| Ibuprofen | Mice | 30 mg/kg— 4.7 ml Children's Motrin in 500 ml water | Daily | No |
| Ibuprofen | Rats | 15 mg/kg— 2.35 ml Children's Motrin in 500 ml water | Daily | No |
| Ketoprofen | Rodents | 5 mg/kg | Daily | No |
*Because of its potential for abuse, use of Buphrenorphine in water would need to be approved by the Office of Regulatory Affairs and done in accordance with all rules regarding controlled substances.
| Injectable Analgesic Options | |||||
|---|---|---|---|---|---|
| Drug Name* | Species | Dose | Route | Frequency | Controlled Substance? |
| Buphrenorphine | Rodents | 0.05-0.1 mg/kg | IM , SC , IP | Daily | Yes |
| Butorphanol | Rodents | 1-2 mg/kg | SC | Every 4 hours | Yes |
| Flunixin meglumine(Banamine) | Rodents | 2.5 mg/kg | SC | 1-2X per day | No |
| Ketoprofen | Rodent | 5 mg/kg | SQ | Daily | No |
| Morphine | Rodents | 5 mg/kg | SQ | Every 2-4 hours | Yes |
| Carprofen | Rodents | 5-10 mg/kg | SQ | Daily | No |
| Meloxicam | Rats | 1.0 mg/kg | SQ | Daily | No |
* Ketoprofen and Buphrenophine are used as injectable drugs with good pain relieving capacities. Please consult an RAR veterinarian with any questions.
Standard Analgesic Drug Selection
Ibuprofen has been recommended for use as a pain reliever with a wide ranging dose of 7.5 to 30 mg/kg (Jenkins, 1987, “Pharmacological Aspects of Analgesic Drugs in Animals: An Overview”, JAVMA 191 (10) pp. 1231; Liles, JH and Flecknell, P, 1992 “Use of NSAID for Relief of Pain in Rodents and Rabbits” Lab Animal 26: p. 241-255). Accordingly, RAR will begin using this drug more routinely as an additive to water to treat mild to moderately painful conditions such as skin lesions, fight wounds and eye abscesses. Carprofen will also be available for use in water as an alternative. Other drugs should be used when severe pain is anticipated. A neophobic response has been documented when adding drugs to water of rats which can cause weight loss but is usually temporary. (“Regarding the Inadvisability of administering postoperative analgesics in the drinking water of rats (Rattus norvegicus)” Speth, Robert C., Smith, Susan, Brogan, Rebecca S. Contemporary Topics In Laboratory Animal Science, 40 (6), 15., Nov. 2001).
Additional Characteristics of Chosen Analgesic Drugs
Ibuprofen
Ibuprofen has anti-inflammatory, analgesic and an anti-pyretic (fever) activity. Ibuprofen is a non-specific COX inhibitor resulting in decreased prostaglandin formation. It is well absorbed orally and the majority is excreted in the urine within 24 hours with a small amount also excreted through the stool. Excretion is virtually 100% within 24 hours of the last dose. Possible side effects include gi ulceration, blood thinning effects (avoid use with blood thinning drugs), decrease in efficacy of blood pressure lowering drugs, and an interference with secretion of lithium and aminoglycosides that can result in increased blood levels of those drugs. At higher doses, some renal effects may be seen as well. No studies of effects in pregnancy have been completed (pregnant humans only use it on advice from their doctors) and it is excreted in small amounts into milk.
Carprofen
Carprofen (Rimadyl) is a relatively new drug which has been used in water but has not been scientifically proven to be effective in this route.. (It has, however, been shown to be effective when delivered in jello – Flexnell, 1999 “Comparison of the Effects of Oral or Subcutaneous Carprofen or Ketoprofen in Rats Undergoing Laparotomy” Veterinary Record 144(3): 65-7). Carprofen is a NSAID and has a much more selective effect than Ibuprofen (inhibits COX 2 while allowing COX 1 activity) which protects the GI system while still being effective in lowering pain. In normal dogs, doses up to 10X the recommended dose resulted in little adversity. Animals with chronic disease appear to be most at risk for developing toxicity with this drug. Effects such as gi problems, hepatocellular damage, renal disease, blood thinning effects on platelets activity, and hypoalbuminemia have been reported. Recommended dose is 5-10 mg/kg orally (Plumb Veterinary Drug Handbook, 4th Edition, 2002).
Meloxicam
Another new NSAID that is available for oral use is Meloxicam. It is expensive and thus may not be practical for every day use but it also shows a more selective inhibition of COX 2. A dose of 1.0 mg/kg orally or subcutaneously once a day for rats has been given.
Jello Formulation and Use
Jello is used as a way to get an effective dose in all at once for pain relief. Since rats and mice are neophobic, they must be introduced to it for several days before it is needed. Once they try it, they like it. The jello is prepared according to the package directions for Jigglers (with the appropriate amount of drug mixed into the water added) and can be poured into ice cube trays to solidify.
| Jellow Recipes | ||||
|---|---|---|---|---|
| Drug Name | Species | Amount of drug | Amount of water | Dose per animal |
| Carprofen | Rat | 100 mg crushed | 500 cc | Yields 0.2 mg Carprofen /ml--at 5 mg dose give 7.5 ml (1.5 tsp) jello cube, at 10 mg dose give 15 ml (1 Tbsp) jello cube |
| Buphrenorphine* | Mouse | 0.3 mg (one ml vial) | 15 ml water | Give 1 cubic ml BID |
| Buphrenorphine* | Rat | 0.3 mg (one ml vial) | 3 ml water | Give 4 cubic ml cube BID |
*Buphrenorphine is a controlled narcotic drug. Because of its potential for abuse, use of Buphrenorphine in jello would need to be approved by the Office of Regulatory Affairs and done in accordance with all rules regarding controlled substances.
Other Resources:
- National Institute of Health, Office of Animal Care and Use "Anesthesia/Analgesia Formulary”
(Tables of drugs commonly used at the National Institutes of Health for pre-anesthesia, anesthesia, analgesia, sedation, tranquilization, and restraint of laboratory animal species) - Huerkamp, Michael J., “The Use of Analgesic in Rodents and Rabbits” Emory University, website, updated August, 2005.
- Flecknell P.A. 1996. Anaesthesia and analgesia for rodents and rabbits. In: Handbook of Rodent and Rabbit Medicine, Laber-Laird K, Swindle MM and Flecknell PA, eds., Pergammon Press, Butterworth-Heineman, Newton, MA, pp. 219-37.
Updated April 1, 2008 by SAK