IACUC Guidance on Categorizing and Minimizing Pain and Distress

Background, Assumptions and Definitions

The Institutional Animal Care and Use Committee strives to support UCI as a world-class research facility.  As stewards of animal welfare, the committee recognizes its role in facilitating a deeper understanding concerning  the importance of identifying and minimizing pain and distress associated with research procedures in live animals.

Pain

Pain is an aversive sensory and emotional experience associated with actual or potential tissue damage. Because animals cannot verbally report pain, it must be inferred from the nature of the procedure and from species-appropriate behavioral and physiological indicators. Procedures that would be expected to cause more than slight or momentary pain or distress in humans should be assumed to cause pain in animals and managed with appropriate anesthesia or analgesia unless scientifically justified and approved by the IACUC.

Distress

Distress refers to an aversive state in which an animal fails to cope or adjust to one or more, often persistent, stressors in its environment.

Pain Categories

Corresponding to the USDA reportable pain category columns (APHIS Form 7023), UCI recognizes the pain categories as follows:

  • Category B:  Animals not subjected to any procedure other than genotyping. Includes those held for breeding, or future research use, as well as those produced in breeding colonies but not used for research purposes (e.g., culled littermates).
  • Category C:  Animals subjected to procedures that may produce momentary, transient pain or distress.
  • Category D:  Animals subjected to procedures that involve pain or distress, and are  performed using anesthesia, analgesia, tranquilizing drugs, or other methods to alleviate pain and distress.
  • Category E:  Animals subjected to procedures without adequate and appropriate anesthesia, analgesia, tranquilizing drugs, or other methods to alleviate pain or distress.  This category also includes animals that may experience painful or distressing disease processes, and which do not receive any of the interventions listed above.

General Guidance Regarding the Categorization of Pain/Distress

Procedures and disease models that produce more than momentary pain or distress are an unavoidable part of research with animals; such procedures require the appropriate use of sedatives, anesthetics, or analgesics, unless withholding of such agents is scientifically justified in writing and approved by the IACUC.  All potentially painful or distressful procedures must be identified in the Animal Use Protocol; the protocol must include criteria that will be used to assess pain and distress in the animals and describe the actions that will be taken to minimize it, such as the use of anesthesia and analgesic agents, housing and husbandry variations, and identification of alternative humane endpoints.  Consultation with ULAR veterinarians is strongly recommended.

Guidelines and Examples:

Category C

Procedures involving momentary, transient, or no pain and distress that typically do not require the use of pain-relieving drugs or other interventions.

Examples:

  • Intravenous, subcutaneous or intraperitoneal injections
  • Venous blood collection
  • Gavage
  • Stimuli that produce only transient pain and/or are escapable or avoidable (e.g., mild foot shock)
  • Behavior testing without aversive stimuli
  • Injections, including euthanasia agents

Category D

Procedures involving more than momentary pain or distress that is alleviated by  anesthesia, analgesics, or tranquilizing drugs.  In addition to analgesia, palliative methods can be used to relieve symptoms without dealing with the cause of the condition. Several husbandry variations (softened food, water accessible from the bottom of the cage, extra bedding) may be used as palliative methods to reduce pain/distress. Other palliative methods require review and approval by the IACUC.

Examples:

  • Surgical procedures (survival or terminal), in which animals received appropriate anesthetics and analgesics
  • Disease or injury models, where animals received appropriate anesthetics and analgesics, including tumor induction, induced infections, Freund’s complete adjuvant
  • Exsanguination under general anesthesia

Category E

Procedures involving pain or distress, where the use of anesthetics, analgesics, tranquilizing drugs or other palliative methods would compromise the experimental design or study results.  Category E procedures require strong scientific justification in the animal use protocol.

Examples:

  • Any Category D procedures are considered "Category E" if analgesics, anesthesia, or tranquilizing drugs must be withheld for experimental reasons
  • Untreated controls in pain studies
  • Paralysis or immobilization of a conscious animal
  • Food or water restriction which reduces the animal’s weight by more than 15% of normal age-matched controls
  • Applying  noxious stimuli that the animal cannot avoid/escape
  • Exposure to extreme environmental conditions

Additional Guidance

The IACUC acknowledges that the impact of procedures may be hard to categorize (e.g., brief anesthesia used to temporarily restrain an animal) and will work with individual researchers to make pain-category determinations on a case-by-case basis.

Occasionally, situations will occur in which the actual pain/distress categories experienced by the animals is different from what was predicted in the animal use protocol; in these cases, the animals should be reported in the Annual Review in the category most consistent with the animal's apparent experience of pain.

References