The Dilemma of Definitions

As has been stated many times, much of the difficulty in achieving a broadly accepted approach to categorizing, and then addressing, pain and distress is due to the absence of a concise definition. From a behavioral perspective, this inability to arrive at a “Webster’s Dictionary” type of definition is due in part to the fact that: 1) pain and distress are not discrete states, but are a continuum of experience; 2) signs differ between species, and most animals hide signs of pain because such a sign of weakness may provoke an attack from predators or subordinate members of the group; 3) there is a lack of specific behavioral indicators of pain; 4) interobserver variability can be large; and 5) there is a tendency to anthropomorphize, which is encouraged by US Government Principle IV. That principle states that “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.”

Issues with Assessing Pain

It is a well-established and accepted practice to use human experience to judge an animal’s experience of pain and distress. Although I completely support this principle, I think we need to use this kind of assessment as a starting, not an end, point. We need to encourage investigators to include studies of pain and distress as they perform their research and to publish their findings.

Currently, there are several variables associated with pain assessment:

1. Assessments vary with the scale used, and they can be very subjective. What one person may view as a procedure that evokes moderate pain or distress, another may view as one that elicits minor pain or distress.
2. As Flecknell (1994) has noted, the absence of preprocedural scoring results in a lack of validation scores. There are no control data, so frequently confounding variables (such as those produced by analgesics) cannot be identified. For example, some of the consequences of surgery in rats, such as loss of body weight and suppression of food and water intake (signs frequently interpreted to be indicative of pain and/or distress), can also be produced in normal, unoperated rats by administration of opioid analgesics.
3. Chronic signs can be subtle and hard to detect. Changes in behavior due to pain and/or distress can be slow, incremental, and, individually, virtually undetectable. Whereas,
4. The dramatic, sudden onset of signs of pain is readily recognizable.

Issues with Assessing Distress

Distress is a generic term that can encompass anxiety, fear, boredom, frustration, and so forth. Thus, there are potentially multiple expressions of distress. Causes of distress that have been proposed include heat, light, sound, thirst, hunger, pain, novelty, exercise, pursuit, disease, and so there are also potentially multiple causes. But remember, the difficulties we continue to have in defining psychological well-being are due to a lack of direct reporting of the state of well-being by the subject (no language), not knowing what minor changes in well-being really mean to the animal, and not knowing what the impact is of levels of well-being on the research (which probably varies with the study).

There are advantages to using animal behavior as an assessment tool. For example, behavioral assessment is probably the least intrusive measure; and in the hands of a skilled, knowledgeable observer, behavior as an indicator of well-being (or lack thereof) can be reliable and powerful. A knowledgeable observer has the expertise to use different criteria in different species and to gauge their significance, and the skilled observer will predicate his/her assessment on the animal’s milieu, including its physical environment, the research it is used in, and the animal’s own status (e.g., its age and health).

However, there are also some disadvantages to using animal behavior as the assessment tool. Early experience (which may not be known), age, and physiological state can influence the behavioral response of an animal leading to interand intra-animal variability. For example, some research indicates that young animals are more responsive to pain stimuli than older animals and that sick animals may also be more responsive than healthy counterparts.

As has often been noted, correlations of specific pain-related behavior with intensity of the pain experience cannot be made. There is no behavior expressed by animals that indicates the severity of pain being experienced. Even the assessment of the efficacy of an analgesic is based on rather crude analgesiometric tests such as a hot plate or tail flick test.

There are too many amateur behaviorists, which can lead to overconfidence in their abilities. One lecture or even one course in animal behavior does not turn someone into an expert, just as the college courses I took in accounting and economics did not turn me into an Alan Greenspan. Our exposure to animal behavior through the popular press and television lulls us into a belief that we all have knowledge in the field and skills in understanding animal behavior.

Indicators of Pain

When evaluation criteria for pain are sought, a common approach is the use of general behavior that is extrapolated into indicators of pain in several species of laboratory animals. The problem is that this approach is rife with subjective criteria and/or contradictions. For example, Morton and Griffiths’ (1985) seminal article, “Guidelines on the Recognition of Pain, Distress and Discomfort in Experimental Animals and an Hypothesis for Assessment,” which has influenced numerous working group reports and reviews over the years, includes a table of specific, summarized behavioral signs indicative of pain and distress. Categories of behavioral criteria used by the authors are posture, vocalizations, temperament, locomotion, and other. Several of the behavioral criteria, such as dormouse posture, anxious glances, hangdog look, urgent squealing, and distinctive cry, are clearly open to a wide range of possible interpretations.

As recently as this year, a publication in ILAR Journal by Carstens and Moberg (2000) attempts to refine the Morton and Griffiths table by blending in elements from the NRC report Recognition and Alleviation of Pain and Distress in Laboratory Animals (1992); the FELASA working group report on “The Assessment and Control of the Severity of Scientific Procedures on Laboratory Animals” (Wallace and others 1990); and a Laboratory Animal Science article by Soma (1987) on assessing pain and distress. Carstens and Moberg propose different categories of criteria: general behavior, appearance, and physiology. This broader evaluation scheme may be more reliable than basing a judgment solely on one type of measure; however, it too contains some inherent difficulties for the evaluator. Specifically, the behavioral signs the authors report as indicators of pain in animals of the same species can be diametrically opposed; yet, both can be observed during experiences of pain. For example, the rat may express reduced activity or increased aggression; the guinea pig may squeal and stampede or go quiet; the dog may whimper, howl, growl or become quiet; and the cat may hiss or spit or become quiet. These inherent contradictions underscore the point that no single behavior is a reliable indicator of pain and that gauging pain requires a skilled observer not only to accurately record the signs but also to interpret them correctly.

It should be noted that behaviors used to assess pain are also not expressed exclusively during painful episodes (e.g., vocalizations). Stafleu and others (1992) make this point using the example of pig vocalizations. If you have ever worked with swine, you are aware that a minimum of restraint, sometimes even simply picking up a piglet, can result in very intensive screaming by the animal. Is the pig in pain? No. Stafleu and colleagues suggest that because piglets run a great risk of being crushed by their mother, they have evolved a low threshold for screaming to alarm the mother. The screaming might indicate some stress (“anxiety”), but even that behavior cannot be judged on this one measure. In addition, of course, the fact that pigs scream rather readily should not lead to the assumption that they are never in pain when they scream. Vocalizations are simply not a sufficiently sensitive measure to use solely in an assessment of pain.

Indicators of Distress

Indicators of distress are no less complex. Expressed behaviors that vary from the norm are generally used as indicators of distress. However, the observer must first establish what is normal for the animal (e.g., free-ranging vs. captive, aged animal vs. young animal) and then determine whether the behavior is not only atypical, but also maladaptive. This distinction is important because it is the expression of maladaptive behaviors that is likely to reflect a detriment in the well-being of the animal (e.g., high levels of locomotion vs. locomotion to the point where the animal is nonresponsive to potentially important external signals). Several scientific studies suggest that the expression of some atypical behaviors may be a coping mechanism of the animal either to increase or decrease its sensory input. Although this expression may signal that reevaluation of the animal’s environment is necessary, such coping activity may actually be an indicator of a lack of distress (Novak and Suomi 1988).

If the behavior profile expressed by the animal is narrow, it is important to identify which behaviors are lacking and whether their lack is a problem for the animal. One should ask what it means to the animal if certain behaviors are not performed. The animal should also be evaluated for changes in its behavior. Several small, incremental changes over time can result in an animal expressing significantly different behavior. Again, what does the change mean to the animal? Change in behavior should not necessarily be equated with behavioral pathology.

Degrees of Stress

As previously mentioned, stress is a continuum of experience. I would consider a mild stressor one that results in a short-term physiological response on the part of some animals and slight to no behavioral adjustment. Examples might include room entry and regular husbandry activities which have been shown to cause an increase in heart rate (Line and others 1989). A moderate stressor may include a minor procedure on the animal or a more significant procedure that is accompanied by pain relief and perhaps unconsciousness during the procedure. A moderate stressor would evoke behavioral adjustment on the part of the animal and physiological recovery or adaptation by the animal. The animal may experience limited distress (or perhaps eustress) associated with restraint. A severe stressor is one for which no relief is provided to the animal either through the ability to physically remove itself from the stressor or by modifications in its environment that would reduce the stress (e.g., use of nesting material to modulate cage temperature or treatment of a disease state). In such a case, there is inadequate adaptation by the animal to the stressor and distress results. I would, therefore, define distress as a state in which the animal is unable to adapt to the stressor and the animal may exhibit maladaptive behavior. The animal is not coping—behaviorally or physiologically.

Using Behavior to Assess Pain and Distress

So, how can we successfully use behavior as an indicator of pain and/or distress? I concur with the literature that recognizes two critical factors: (1) Individuals making the behavioral assessments must be knowledgeable and skilled in the interpretation of behavior; and (2) assessments should not be influenced by the personal biases of the observer (i.e., what the animal is perceiving vs. what the observer is feeling when observing the animal [Sanford and others 1986]).

Thus, behavior should be just one assessment tool used in the process by which pain and distress are assessed, monitored, and relieved. An overarching precept is that performance standards should be used in the assessment balanced with our scientific knowledge of animals’ behavior.

A workable process for pain and distress management involves use of the IACUC. Specifically,

• The IACUC should review protocols for the appropriate use of pain-relieving agents.
• The committee should consider the criteria and determine a process for timely intervention, removal of animals from the study, or euthanasia if painful or distressful outcomes are anticipated.
• The committee’s deliberations should be documented.
• The IACUC should ensure that a system to monitor and provide feedback is in place so that modifications in procedures can be requested as necessary.
• Guidelines should be in place that provide assistance in categorizing pain and/or distress for use by investigators and IACUC members.
• A classification system should be reasonable and consistently applied throughout the institution.
• A mechanism for prompt reporting of compromised animals should be developed and implemented.
• Personnel (research staff, animal care staff, IACUC members) should be trained in pain and distress management.

A Program of Pain and Distress Management

I believe our focus and that of the USDA needs to be on the experience of the animal. We should consider an entire program of pain and distress management, of which the animal’s behavior will likely play a role in each of the following program elements: recognition, assessment, relief (if possible), and a feedback loop to animal care and use.

Responsibility for and oversight of animal well-being—and more specifically the minimization of pain and distress—is shared by several key institutional components: the research staff, the IACUC, the veterinarian, and other animal care staff. Their roles are separate, yet they overlap. There should be a flow of information and synergy among these components that results in a strong program to identify potential pain or distress-inducing circumstances, implement change (where possible) to minimize/eliminate the pain or distress, and include follow-up and monitoring to ensure that the goals of minimization are achieved. It is critical to avoid a splintered program in which these various institutional elements operate in different directions, rather than building and supporting a uniform, cohesive, and proactive program of pain and distress management.