Distress in humans may be more widespread (or at least more readily recognized) than that observed in nonhuman animals because of unique human cognitive capacities, such as the ability to clearly communicate threatening, dangerous, or painful conditions; to remember these circumstances and their consequences over extended periods of time; and to apply the emotions engendered to other stimuli on the basis of verbal or categorical concepts (Sapolsky 1994). A substantial proportion of the American population will at some point suffer from an illness that is distressing or even incapacitating (e.g., depression or a severe anxiety disorder). Many of those afflicted present with no specific experiential basis for their disorder, which suggests that our society’s efforts to prevent and/or control intense and chronic stressors, even if relatively successful, may not prevent these maladies.

A significant portion of research with laboratory animals deals with pathology resulting in distress, incapacitation, or death for the animals. While it is often possible to study incapacitating or lethal conditions while using palliative agents or euthanasia in order to alleviate or preclude animal distress, it is not possible to adequately investigate distress itself without allowing it to occur. While it is therefore desirable to reduce distress in laboratory animals, this should not extend to eliminating all of it. Animal models have provided insight into the anatomical and molecular bases of various human distresses (Blanchard and Blanchard 2005; Herman et al. 2005; Maier and Watkins 2005; Phelps and LeDoux 2005). An attempt to totally eliminate the study of distress would imply abandoning the major goal of biomedical research: to understand and find therapeutic solutions for conditions that continue to plague a significant portion of humanity as well as nonhuman animals.

With care and attention, it should be possible to attain the optimum goal of reducing distress even while continuing to investigate it. When using procedures that intentionally result in distress, the investigator, in consultation with the veterinarian and the IACUC, should develop a plan that will establish limits to the levels of distress allowed. Appropriate methods include measures to alleviate distress following completion of the procedures or attainment of the research aims (e.g., maximum allowable weight loss as a percentage of normal body weight). In line with the important goal of extrapolating such research to specific human conditions or disease states, the limits chosen should be sensitive to the goals of the research project and the wider scope of distress-related phenomena to which the project is potentially relevant.

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