clinical phenotype). It is critical to recognize and manage animal pain and distress.

The International Association for the Study of Pain has defined pain in humans as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (Mersky, 1979). Although animals cannot communicate verbally, they exhibit motor behaviors and physiologic responses similar to those of humans in response to pain. Those behaviors may include simple withdrawal reflexes; complex, unlearned behaviors such as vocalization and escape; and learned behaviors such as pressing a bar to avoid further exposure to noxious stimulation. However, there are species-specific behaviors that animals may express in response to pain (Bolles, 1970), see Table 2-1 for review.

Stress (or the stress response) has been defined as “the biological response an animal exhibits in an attempt to cope with threats to its homeostasis” (Stokes, 2000). Threats to homeostasis are called “stressors.” Stressors can be physical, environmental, or psychologic in origin (NRC, 1992), and adaptation can involve immunologic, metabolic, autonomic, neuroendocrine, and behavioral changes (Moberg and Mench, 2000), but the type, pattern, and extent of the changes depend on the stressor involved. When the animal responds to a stressor in an adaptive way, the animal returns to a state of comfort. It is also possible for stressors to induce responses that have beneficial effects (Breazile, 1987). Animals (and people) are normally exposed regularly to stressors to which they need to respond and adapt (Sapolsky, 1998), and some stress is probably necessary for well-being (NRC, 1992).

When an animal is unable to completely adapt to a stressor and the resulting stress, an aversive state has developed defined as distress. The term distress encompasses the negative psychologic states that are sometimes associated with exposure to stressors, including fear, pain, malaise, anxiety, frustration, depression, and boredom. These can manifest as maladaptive behaviors, such as abnormal feeding or aggression, or pathologic conditions that are not evident in behavior, such as hypertension and immunosuppression (NRC, 1992).

Regulatory Oversight

Extensive guidelines, policies, and regulations govern the management of pain and distress in laboratory animals. The US Government Principles (IRAC, 1985) state:

Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals [Principle IV].

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