Female- and intruder-induced ultrasonic vocalizations as proxy indicators for animal well-being and postoperative pain recognition in C57BL/6J mice

Abstract

Mice are the most commonly used research animal and often undergo painful procedures. It is important to minimize pain and distress in research animals. However, recognizing pain and distress in mice is challenging. There is a need for new objective techniques to assess pain, distress, and animal well-being in laboratory mice. Female urine-induced male mice ultrasonic vocalizations (FiUSV) are ultrasonic vocalizations produced by adult male mice following presentation of adult female urine, while intruder-induced ultrasonic vocalizations (IiUSV) are produced by resident adult females when interacting with an intruder female mouse. These affiliative behaviors may be reduced with pain, distress, or decreased well-being. Two studies were completed to determine if FiUSV and IiUSV can be used as proxy indicator assays to assess animal well-being and postoperative pain in mice. First, the role of FiUSV and IiUSV in identifying decreased animal well-being were assessed in mice using an acute inflammatory sickness model. Second, using a vasectomy pain model, the role of FiUSV in detecting postoperative pain was assessed in male mice. Findings from the first study showed mice injected with lipopolysaccharide (LPS) intraperitoneally produced significantly fewer FiUSV and IiUSV compared to saline-injected mice, and the decrease in the number of USV occurred prior to showing overt clinical signs of sickness. In the second study, vasectomized mice given no postoperative analgesics produced fewer FiUSV compared to baseline, while vasectomized mice given postoperative analgesics had no change in the number of FiUSV compared to baseline. The findings from these studies provide evidence that FiUSV and IiUSV can be used as proxy indicator assays to assess animal well-being associated with acute inflammatory sickness, and FiUSV can be used to assess postoperative pain.