Relieving Pain for Rodents in Research

By Michele Cunneen, AWI Laboratory Animal Consultant

There is an increasing tendency in animal research to ask the question, "Why not?" For a long time whenever this question was asked in the context of improving animal welfare, the response from the scientist was, "It will interfere with the model and confound the results." However, if the purpose of the research on animals is to cure or treat human disease, and a human with such a disease would take some form of pain relief in addition to whatever treatment is contemplated in the research, then isn’t the animal used in research entitled to this same relief?

Admittedly, there are early stage processes where provision of pain relief might affect the results. However once you move to a screen of a specific disease, this excuse for withholding pain relief is no longer legitimate. The data suggest that stress and pain can have just as much if not more adverse effects on the models as steps taken to relieve the stress or pain. This has led to a growing movement to require analgesics in cancer and arthritis studies involving rodents.

In this context, analgesic drugs must have effective pain relieving qualities without impacting the cellular processes of the model, in particular inflammation. Two drugs - buprenorphine and metamizole (dipyrone) - satisfy these criteria, with demonstrated efficacy in relieving rodent pain without anti-inflammatory effects that could confound results. As such, they have been used in an increasing number of animal facilities as standards of care in cancer and arthritis models.

Another factor affecting animal stress levels is the method by which the analgesic is administered. With regard to the above-mentioned analgesics, the most common routes for buprenorphine are oral and subcutaneous; for metamizole, they are oral and intravenous. In long term studies oral administration of the compounds is both a time saver and less stressful to the animals.

If administered orally, stress may be further reduced by use of a non-gavage method, such as adding the drug to the animals' food. This method requires preparation and attention to the nature of the food paired with the drug, however. In order to be successful at oral soft food dosing, animals must be pre-study acclimated. The animals must know and like the untreated food. The delivery food must be soft, moist and highly preferred. Plain chow that has been wetted will not work. Commercial entities such as Bioserv, Lab Diet and Clear H2O have soft diets available, or they can be homemade using flavored gelatin with chow. Regardless of the chosen route, lab personnel concerned with animal welfare should take note that best practices are moving towards the standard use of analgesics.

References:

Fish, R., Danneman, P.J., Brown, M., & Karas, A.Z. (Eds.). (2008). Anesthesia and analgesia in laboratory animals (2nd ed.). Boston: Academic Press.

Milano, J. et al. (2008). Antinociceptive action of 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester in models of inflammatory pain in mice. Life Sciences, 83, 739-746.

Munoz, J. et al. (2010). Synergism between COX-3 inhibitors in two animal models of pain. Inflammopharmacology, 18, 65–71. EMEA (European Medicines Agency). (2003). Metamizole: Summary report (2) - Committee for Veterinary Medicinal Products (EMEA/ MRL/878/03-FINAL). London: The European Agency for the Evaluation of Medicinal Products.