Refinement Alternatives

Analgesia and Pain

Pain

Pain is an unpleasant sensory and emotional experience associated with actual or potential damage, or described in terms of such damage. Animals must not be subjected to unnecessary pain or distress. The experimental design must offer them every practicable safeguard, and if pain or distress is a necessary or unavoidable part of the study, it must be minimized both in intensity and duration.

In most cases, analgesic drugs can be administered to manage pain. It is the position of the American College of Veterinary Anesthesiologists (ACVA) that "it is preferable to empirically administer analgesics pre-emptively if there is any question that a procedure will induce pain in an animal." Successful alleviation or prevention of pain in laboratory animals is critically dependent upon three factors:

  • accurate assessment of the degree of pain experienced, or likely to be experienced, by the animal;
  • the implementation of effective methods of pain control; and
  • integration of pain control measures with specific research protocols.

Pain assessment in terrestrial animal species

Species-specific and individual responses to pain are quite variable; therefore, it is essential that veterinary and animal care staff evaluating animals for pain have a thorough understanding of typical species-specific and individual behaviours. An important part of this is the ability to recognize changes in the normal behaviour and appearance of the animal.

Examples of clinical signs (observable without handling the animal) that may indicate pain in terrestrial species are:

  • changes in personality or attitude;
  • abnormal vocalization, especially when a painful area is palpated or the animal is forced to move;
  • licking, biting, scratching or shaking of a painful area;
  • changes in the appearance of the coat;
  • changes in posture or ambulation;
  • changes in activity level;
  • changes in appetite, such as a decrease in food and water consumption, leading to weight loss and dehydration;
  • changes in facial expression;
  • excessive sweating or salivation;
  • Ocular or nasal discharge;
  • Teeth grinding; and
  • Changes in bowel movements or urination.

Other clinical signs (requiring the animal to be handled) that may be indicative of pain include: increases in heart rate, respiratory rate and body temperature, and elevations in blood glucose, corticosteroid and catecholamine concentrations. The diagnosis of pain in veterinary medicine is seldom made on the basis of a single observation or laboratory value. Instead, it is subjective in nature, and is dependent on a combination of a clinical examination undertaken by an experienced individual; familiarity with species, breed, and individual behaviour; knowledge of the degree of pain associated with particular procedures or illnesses; and recognition of the signs of discomfort and pain.

Regardless of the clinical signs demonstrated, if there is any doubt that an animal may be experiencing pain, then a trial treatment with analgesics should be initiated.

Pain assessment in fish

Fish have the potential to experience pain, and manipulations that provoke stress or avoidance/escape behaviour may be causes of distress. Fish respond to noxious stimuli (stimuli that are damaging or potentially damaging to normal tissue, such as mechanical pressure, extremes of temperature and corrosive chemicals) with altered behavioural, physiological and hormonal parameters.

However, the recognition and evaluation of pain in fish is not easy. Many fish species are prey animals and are genetically predisposed not to exhibit signs of injury or pain. Although fish lack some of the structures associated with pain perception in mammals (e.g., well-developed cortex and neospinothalamic tract), there exists evidence that fish respond in a similar manner to noxious stimuli, learn to avoid "unpleasant" experiences, and respond with an amelioration of pain response after treatment with morphine.

Examples of clinical signs of pain in fish are:

  • changes in eye condition, fin and skin condition, mucus production, and/or colour;
  • changes in feed consumption;
  • changes in feeding activity;
  • changes in respiratory rate;
  • changes in the individual's position in the water (upright, upside down, tilted, etc.);
  • changes in social interactions, such as direct attacks, domination of choice tank locations, schooling, and social isolation;
  • lack of response to external stimulation;
  • hyperactivity or hypoactivity;
  • abnormal movements such as flashing or scraping the body;
  • unexpected jumping or escape behaviour; and
  • avoidance reaction to mechanical prod or light beam.

Other signs that are indicators of acute stress and that may be indicative of pain include changes in corticosteroid and catecholamine levels, as well as increases in plasma glucose and lactic acid.

Regardless of the clinical signs demonstrated, if there is any doubt that a fish may be experiencing pain, then a trial treatment with analgesics should be initiated.

(This section was adapted from the ACVA position paper on the treatment of pain in animals and the CCAC guidelines on: the care and use of fish in research, teaching and testing).

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Analgesia and pain control

Animal pain assessment is difficult and time-consuming to implement effectively; thus, it is tempting to simply give all animals a standard dose of analgesic. In humans, the use of such fixed dose regimens has been identified as one of the factors contributing to inadequate pain management, so this approach should be avoided when dealing with animals.

Instead, treatment of pain should be tailored to the individual animal, and should be based, in part, on the species, breed, age, procedure performed and degree of tissue trauma, individual behavioural characteristics, degree of pain, health status, and availability of drugs and techniques. Selection of the most appropriate analgesic drug or technique requires professional veterinary judgement.

To control animal pain, it is important to:

  • administer an appropriate analgesic that provides the required intensity of pain relief (drugs with known analgesic properties are opioids, a-2 agonists, local anaesthetics, and nonsteroidal anti-inflammatory (NSAID) drugs);
  • consider use of a combination of analgesic drugs from different drug classes (i.e. multi-modal analgesia) that may greatly enhance analgesic effects while allowing for reduced dosages and minimizing adverse effects;
  • consider administering analgesic drugs before the onset of pain (pre-emptive analgesia) to allow for better control of pain during the postoperative period;
  • administer the analgesic at an appropriate dose;
  • monitor the animal carefully and modify the dose or frequency of administration as needed;
  • continue administration of the analgesic at appropriate time intervals;
  • stop administering the analgesic at an appropriate time after surgery; and
  • ensure that non-pharmacological approaches to alleviating pain in animals are suitable (e.g., good husbandry practices and nutritional support).

(This section was adapted from the ACVA position paper on the treatment of pain in animals and the NC3Rs website).

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Pain control and research protocols

When planning an experiment, investigators should first consult with their institution's clinical veterinarian regarding integration of pain control measures in the research protocol. To effectively implement refinement into their animal use protocols, investigators should:

  • adapt existing methods of pain assessment for the species to the requirements of the particular research procedure being undertaken;
  • if methods of pain assessment are not available, consider devoting resources to developing some form of scoring system;
  • if pain scoring is not possible, determine the analgesic protocol based on clinical experience with other surgical procedures in that species;
  • if possible, use dose rates that have been established using studies that have employed pain scoring systems;
  • when data on pain scoring is not available, estimate doses from results of analgesiometric studies using tonic (longer lasting) nociceptive stimuli (e.g., late phase formalin test);
  • use pre-emptive analgesia and multimodal strategies; and
  • attempt to evaluate the efficacy of the analgesic regimen selected, if only by clinical assessment.

Pain control problems have been recognized when dealing with pain in companion animals, farm animals, and zoo and wild animals, and this is an area in which rapid developments are underway. It is therefore important to regularly review pain management procedures to ensure they represent current best practice. Finally, whichever method of pain control is employed, it must be integrated into an overall scheme of peri-operative care.

(This section was adapted from the NC3Rs website).

For more information on analgesia and pain the following resources may be useful:

CCAC resources
Online articles

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Online resources
Other publications
  • Flecknell P. & Waterman-Pearson A. (2000) Pain Management in Animals . 180pp London: W.B. Saunders.
  • Kohn D.F., Martin T.E., Foley P.L., Morris T.H., Swindle M.M., Vogler G.A. & Wixson S.K. (2007) Guidelines for the assessment and management of pain in rodents and rabbits. Journal of the American Association for Laboratory Animal Science 46:97-108.
  • Weary D.M., Niel L., Flower F.C., & Fraser D. (2006) Identifying and preventing pain in animals . Applied Animal Behaviour Science 100:64-76.

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