ABSTRACT
Pain or other forms of distress are important considerations in laboratory animals. While there is a great diversity of views, it is clear that for many, minimization of pain and distress improves acceptability of use of animals in research and testing.1-3 The concept of minimization of harm to animals was described in Russell and Burch’s classic text, The Principles of Humane Experimental Technique,4 and has been subsequently popularized as the “3 Rs” of animal experimentation. These are: Reduction of the number of animals used, Replacement of animals with nonsentient alternatives (or with human subjects), and Renement of experimental design to minimize pain and distress. Renements may include efforts to reduce stress or pain such as training or acclimation of animals and investigators, altered experimental methods, provision of social contact, supportive care, environmental enhancement, increased monitoring for pain and distress in order to intervene or end an experiment, etc. Over time, as we have begun to better understand the assessment and impact of pain and distress, renement has become an increasingly important ethical aspect of animal research. In addition, the alleviation of unnecessary pain and distress may improve the quality of scientic data obtained. The manner in which experimental animals are handled, housed, and fed has an impact on physiological processes such as development, toxicology, oncology, infection, cognition, or cardiovascular status; these and other examples abound in the literature.5-22 Pain and other stressors have been demonstrated to result in production of cytokines and activation of an endocrine state of catabolism, translating into an overall spectrum of effects such as decreased immune responses and healing rates, increases in tumor metastasis retention after surgery, and the development of chronic pain states.23-29 Severe, uncontrolled stress is well known as both a trigger for disease and an impediment to recovery. When the goal of an experimental intervention is to improve disease outcome, the effect of unnecessary stress on subjects is concerning if it might obscure the impact of a studied treatment.30 Pain and distress may represent unrecognized experimental variables that can have signicant effects on research results, and the reduction of painful or distressful experiences can potentially benet both the welfare of the animals used and the scientic output from the project.
