Research Grants 2003-2004

Reducing Postoperative Pain and Distress in Mice

Alicia Z. Karas, DVM
Tufts University, Boston, Massachusetts

A major problem of humane experimental use of animals becomes evident as IACUCS review mouse use Protocols. Investigators who are asked, to provide post surgical supportive care after painful procedures, such as surgery, have relatively little information regarding doses, techniques; and effects Of supportive therapy. Unfortunately, evidence-based studies are comparatively rare. Our group has been studying postoperative behavior and weight changes in mice following surgery, and has developed a model to study interventions that might improve postoperative welfare. Briefly, we videotape singly housed mice in a standard setting, for 5 minute intervals every 3 hours for 48 hours. Using a camera that produces images during the mouse's active period (darknesss), we have demonstrated that typical mouse behaviors; such as reaching for the top of the cage, climbing on the roof of the cage and eating or drinking are markedly attenuated compared to control groups who have had anesthesia only. In addition, they spend significantly more time sleeping and experience weight loss of 8-12% over the initial 24 hours following surgery. We hypothesize that these aberrations result from pain or metabolic stress or both. Furthermore we hypothesize that interventions that reduce pain and that minimize metabolic stress will improve animal well-being as well as the validity of experimental models. Specifically, we hypothesize that the abnormal behavior and weight loss experienced by mice after surgery can be:

rectified by analgesics, supportive therapies, or anesthetic regime and
used as a tool to decipher the amount of stress caused by various experimental procedures performed routinely on mice, and thus to evaluate different techniques.

We will test these hypotheses by

continuing the current work in order to identify one or more analgesic regimens that will reduce postoperative derangements in activity and weight in mouse models of laparotomy and or ovariectomy, and
study of supportive therapies (early postoperative thermal support, fluid and nutritional support) to determine if the weight loss is responsive to non-drug therapies, and
begin to study of five commonly used anesthetic regimens for mice (pentobarbitol, avertin (tribroinoethariol), ketamine-xylazine, isoflurane, and ketamine-isoflurane) in order to evaluate their effect on the postoperative course.

Further evaluation of combination techniques (i.e. anesthetic regimen plus analgesia plus supportive care) will determine optimal postoperative care of mice.