Experiment Guidelines for the Prevention, Assessment and Relief of Pain and Distress in Laboratory Animals

A key aspect of the animal welfare regulations is that pain and distress be minimized whenever possible. Therefore, it is necessary to design and perform experiments in such a way as to prevent the animals from experiencing problems unless is is necessary to achieve the goals of the study (i.e. category "c" studies).

It is not sufficient to merely address these issues in a protocol. The animals themselves must be monitored, and appropriate actions taken if pain or distress are observed. The problem is that assessing pain and distress in animals is not a simple task. Animals may not show signs of pain as readily as would a human being, and they certainly can not communicate it in the same way. There is even great variability among species in the way pain or distress are expressed. In general, animals whose biological niche is that of a prey species (rodents, rabbits, nonhuman primates, livestock) are less likely to alter their behavior in response to pain than would a predatory animal, as doing so would make them a target for predation. In addition, behaviors are often interpreted by humans in the context of our understanding of what that behavior would mean for our species rather than for the species being assessed.

Research Animal Resources animal care and veterinary staff are delegated by the IACUC to serve in the capacity of monitoring for signs of pain and distress in laboratory animals. They are trained and experienced in this area and are a good resource for monitoring the progress of studies. However, investigators must also be aware of signs that an experimentally induced or spontaneous disease is occurring in their animals. They may have more contact with the animals than RAR, and ultimate responsibility for the ethical use of animals lies with the investigator.

The following guidelines are used by RAR, the IACUC and by regulatory agencies to determine if an animal is experiencing pain or distress.

It is assumed that for vertebrates, any procedures that would be expected to cause more than slight or momentary pain or distress in a human being will cause similar pain or distress in an animal, unless scientifically demonstrated otherwise.
Distress is defined as a maladaptive response to a stressor. It is recognized that some stress is normal, but if animals react in such a way that their health is being compromised (e.g. anorexia in response to induced disease or self-aggression in response to psychological stress) this is considered distress..
Certain procedures are always assumed to have the potential for causing pain or distress. These are the basis for the numerous IACUC experimental guidelines that are intended to prevent pain or distress. These include (associated guidelines for these procedures are available by clicking on the highlighted links):

Surgery anesthesia and post-procedural care must be performed in such a way as to prevent pain, infections and other complications

Repeated use of, large volumes of, or intradermal injections of Freund’s complete adjuvant

Intraperitoneal implantation of ascites-producing hybridomas for monoclonal antibody production

Prolonged (greater than 1 hour) physical restraint

Malignant neoplasms

Prolonged food or water deprivation

Distal tail biopsy in animals over 3 weeks of age (tail snipping)

Electrical shock or other adverse stimuli that are not immediately escapable

Paralysis or immobility in a conscious animal

Inflammatory disease

Organ failure resulting in clinical signs

Non-healing skin lesions

Whole body irradiation at high doses

Withdrawal of more than 10% of an animal’s blood volume

Studies that require the animal to reach a moribund state or die spontaneously as the enpoint of the study. The earliest endpoint possible should be used to prevent pain or distress.

Animals subjected to these and similar conditions are expected to receive appropriate monitoring and any necessary supportive care, analgesia, or anesthesia to prevent pain or distress.
Despite these precautions, pain or distress may occur as a consequence of a study or a spontaneous disease.

Assessment of pain or distress may be based on many different criteria including:

Decreased activity

Abnormal postures, hunched back, muscle flaccidity or rigidity

Poor grooming

Decreased food or water consumption

Decreased fecal or urine output

Weight loss (generally 20-25% of baseline), failure to grow, or loss of body condition (cachexia)

Dehydration

Decrease or increase in body temperature

Decrease or increase in pulse or respiratory rate

Physical response to touch (withdrawal, lameness, abnormal aggression, vocalizing, abdominal splinting, increase in pulse or respiration)

Teeth grinding (seen in rabbits and farm animals)

Self-aggression

Inflammation

Photophobia

Vomiting or diarrhea

Objective criteria of organ failure demonstrated by hematological or blood chemistry values, imaging, biopsy, or gross dysfunction

Relief of Pain or distress

The RAR veterinarian will consult with the investigator to develop a plan for treatment of animal animal health problems.
If an animal is experiencing unrelieved pain or distress, it must be euthanized.

Additional Resources

[ILAR Journal Animal Well-being: Immune Function, Behavior, Morphology, and Psychoneuroimmunology]

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The information contained in this site is intended as a reference for University of Minnesota investigators, and animal husbandry and veterinary staff. Drug information and dosages are derived from a variety of sources and do not necessarily guarantee safety or efficacy. Information obtained through this site should not be relied upon as professional veterinary advice. Any medications administered or procedures performed on animals should only be performed by or under order of a qualified, licensed veterinarian.