ARC Policy
- Analgesics must be provided to all animals following survival surgery unless scientific justification for withholding post-operative analgesics is provided by the investigator and approved by the ARC, or if a veterinarian examines the animal and determines that analgesic administration is no longer necessary. In cases where post-operative analgesics cannot be administered for scientific reasons, the animals must be listed in Pain Category E (i.e., pain/distress cannot be relieved by use of anesthetics, analgesics, or tranquilizers as the use of these agents would interfere with the experimental design).
- Analgesics must be given such that these agents become effective before the animal emerges from anesthesia. Therefore, analgesia must be administered before surgery and re-dosed as needed during the procedure.
- The use of local pain-relieving drugs such as Marcaine® (bupivacaine), in addition to systemic analgesia, may be indicated for some procedures that will result in significant disruption of the skin (e.g., Alzet pump placement, catheter exteriorization), as these drugs may help to block the onset of the pain cascade due to disruption of the dermal nerve cells. Local analgesics are not intended for use in lieu of systemic analgesics, unless the withholding of systemic analgesia is scientifically justified.
- Major survival surgeries require at least 48 hours of post-operative analgesia, and then as needed if the animal still appears to be in pain. Surgeries that involve the potential for significant pain or distress (e.g., spinal cord transection, bone fracture induction, or open abdominal surgeries) may require the application of multimodal analgesia. A major survival surgery is defined as any procedure that penetrates and exposes a body cavity, produces substantial impairment of physical or physiologic functions, or any procedure that requires the use of more than a single application of a short-term anesthetic.
- Minor procedures require at least 24 hours of post-operative analgesia, and then as needed if the animal still appears to be in pain.
- For guidance on selection and use of analgesics, please contact the Division of Laboratory Animal Medicine (DLAM). Additional detail regarding the various classes of analgesics is included below.
Basis
USDA Animal Welfare Act Regulations §2.31(d)(1)(iv)(A) and (ix): "Procedures that may cause more than momentary or slight pain or distress to the animals will be performed with appropriate sedatives, analgesics, or anesthetics, unless withholding such agents is justified for scientific reasons, in writing, by the principal investigator and will continue for only the necessary period of time...Activities that involve surgery include appropriate provision for pre-operative and post-operative care of the animals in accordance with established veterinary medical and nursing practices."
PHS Policy IV.C.1.a-b: "Procedures with animals will avoid or minimize discomfort, distress, and pain to the animals, consistent with sound research design. Procedures that may cause more than momentary or slight pain or distress to the animals will be performed with appropriate sedation, analgesia, or anesthesia, unless the procedure is justified for scientific reasons in writing by the investigator."
Guide for the Care and Use of Laboratory Animals, p. 120: "An integral component of veterinary medical care is prevention or alleviation of pain associated with procedural and surgical protocols...Pain is a stressor and, if not relieved, can lead to unacceptable levels of stress and distress in animals. Furthermore, unrelieved pain may lead to 'wind-up,' a phenomenon in which pain sensitization results in a pain response to otherwise nonpainful stimuli...For these reasons, the proper use of anesthetics and analgesics in research animals is an ethical and scientific imperative...In general, unless the contrary is known or established, it should be assumed that procedures that cause pain in humans also cause pain in animals."
Considerations Regarding Choice of Analgesics
Pain has been defined by the International Association for the Study of Pain as "[a]n unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. It is always subjective."
The fact that different anatomical and neurobiological substrates for pain exist supports the use of targeted pain therapy and explains the variable effectiveness of analgesic drugs depending upon the characteristics of pain. In the research laboratory setting the characteristics of pain will vary with the particular animal (species, age, strain) and the type of potentially painful procedure.
The following lines reflect a brief description of the mode of action, indication, contraindication and side effects of the most commonly used type of analgesics in the UCLA animal facilities. For alternative options and for dosage and regimen recommendations please contact a DLAM veterinarian.
- p-Aminophenol Derivatives – Included in this group is acetaminophen. Acetaminophen has analgesic and anti-pyretic activity with weak anti-inflammatory action. This drug is contraindicated in cats due to increased sensitivity to toxicosis. Methemoglobinemia and hepatotoxicity characterize acetaminophen toxicosis. Available in the form of tablets, capsules, suppositories, chewable tablets, wafers, elixirs and solutions, in combination with other drugs. Effective against pain of low to moderate intensity; recommended only for minor surgical procedures.
- Non steroidal anti-inflammatory drugs (NSAIDS) – Agents that reduce inflammation and provide analgesia primarily by inhibiting one or more steps in the metabolism of arachidonic acid through inhibition of inflammatory cytokine synthesis. NSAIDs do not contain the molecular steroid ring structure and don’t have the immunosuppressive and metabolic side effects associated with corticosteroids. Most NSAID act primarily to reduce the biosynthesis of prostaglandins (PG) by inhibiting cyclooxygenase (COX). NSAIDs most commonly used in veterinary medicine include:
- Propionic acid derivatives – Ibuprofen, ketoprofen and carprofen are included in this group. Ketoprofen and ibuprofen are available in parenteral form. Carprofen and ibuprofen are available in oral tablets. Ketoprofen and ibuprofen inhibit both isoforms of cyclooxygenase (COX-1 and COX-2), with ketoprofen having a higher selectivity for COX 1 than ibuprofen in dogs. Carprofen is claimed to be predominately COX-2 selective drug, but it does inhibit COX-1 slightly. Efficacy against orthopedic and postoperative pain compares favorably in clinical studies with some opioids such as buprenorphine. Drugs in this group can have GI side effects including GI erosion and altered permeability. Most of these drugs can alter platelet function and altered bleeding time. Carprofen and Ketoprofen did not affect bleeding time in dogs based on previous studies. Carprofen has been reported to cause minor changes in certain renal parameters, but most studies have not observed significant risk to renal function.
- Oxicams – The most commonly used drug used in veterinary medicine in this group is Meloxicam. Meloxicam is available in parenteral, tablet and oral suspension. This drug is a selective inhibitor of COX-2 in humans and dogs and non selective in cats. It is as effective an analgesic as buprenorphine for post-operative pain resulting from soft tissue surgery. Meloxicam does not affect bleeding time in dogs, however there’s no current evidence of this in other species. GI side effects and other typical NSAID toxicities have been reported.
- Nicotinic acid derivatives – Flunixin meglumine is included in this group of drugs. This drug is available in oral and parenteral forms. It demonstrates COX-1 selectivity in dog and horse blood. Flunixin is a potent analgesic agent after parenteral administration in mice, rats and monkeys. This drug demonstrates potency similar to that of other NSAIDS such as ketoprofen and carprofen. The most common potential side effect is gastroduodenal ulceration and perforation.
- Opioids – Opioids are the most effective analgesics available for the systemic treatment of acute pain in many species. Opioids combine reversibly with specific receptors (mu, delta and kappa) in the brain, spinal cord, and periphery, altering the transmission and perception of pain. The clinical effects of opioids vary between the µ opioid receptor agonist, partial mu agonists, and agonist-antagonists. Repeated use of opioids may induce tolerance in some species. The most common side effects associated with the use of opioids include respiratory depression, constipation, sedation, euphoria, dysphoria, excitement and pica. Buprenorphine is a partial mu agonist and kappa antagonist that is widely used in Laboratory animal medicine due to its relatively long duration of action. Buprenorphine is available in parenteral formulation.
References
- Fish, R.E.B., Marilyn J.; Danneman, Peggy J.; Karas, Alicia Z., Anesthesia and Analgesia in Laboratory Animals. 2nd ed. American College of Laboratory Animal medicine Series, ed. A. Press. Vol. 1. 2008, Amsterdam, Boston, Heidelberg, London, New York, Oxford, Paris, San Diego, San Francisco, Singapore, Sydney, Tokyo. : Elsevier. 268-275.
- MERCK, Nonsteroidal Anti-Inflammatory Drugs, in The Merck Veterinary Manual, S.E. Aiello, Editor. 2005, Merck & Co., INC. New Jersey. p. 2131-2137.
- Sam McMillan, V.A., DAVN(Med), RVN. NSAIDS: What are the Options? in British Small Animal Veterinary Congress. 2008. Birmingham, UK: Quedgeley : British Small Animal Veterinary Association 2008.
- Bill, R.P. NSAIDs--Keeping Up With All the Changes, in Atlantic Coast Veterinary Conference 2008. 2008. Atlantic City, New Jersey.
- Budsberg, S.C. Review of NSAIDS: COX Selectivity and Systemic Effects Beyond Analgesia (S22C). in Western Veterinary Conference 2009. 2009. Las Vegas, NV.
Approved 6/9/03; Revised 10/27/03, 11/24/03, 8/24/09; Updated 1/18/11