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OCR for page 49
CHAPTER 3. Recognition and assessment of
pain
This chapter begins with a presentation of the clinical signs and
behaviors used by veterinarians to recognize animals in pain. It then discusses
methods for pain assessment with a focus on techniques developed for specific
laboratory animal species. It concludes with species-specific clinical signs and
behavioral responses to pain.
Introduction
Recognizing pain and assessing its intensity are both essential for its
effective management. If pain is not recognized, then it is unlikely to be
treated. Failure to appreciate the intensity of pain will hamper the selection
of an appropriately potent analgesic, raise doubts about the effectiveness of
the administered dose, and result in less than optimal treatment. In humans,
self-report of pain is the "gold standard" by which other assessment techniques
can be judged, although there are limitations and biases even when using this
approach (see Chapter 1). For animals, as for humans who cannot self-report
(e.g., the very young and those with cognitive impairment; Ranger et al. 2007;
Zwakhalen et al. 2006), other assessment tools are needed. Since the
publication of the first edition of this report (NRC 1992), there have been
considerable advances in our understanding of animal pain and numerous
attempts to develop methods of assessing pain.
Yet few validated assessment techniques are available. In most
circumstances pain is assessed based on an animal’s clinical appearance and
overall behavior. Although this approach can be unreliable, it is usually
effective in detecting severe pain in many species. It is also effective when
pain is localized to one limb (causing lameness) or to a specific body area
(resulting in a marked behavioral response if that area is palpated).
The ability to assess pain will improve with the development of
validated, objective schemes for particular animal species and particular types
of procedures. Some schemes of this type are in development, while others
(e.g., post-surgical pain assessment in dogs; Morton et al. 2005) or pain after
abdominal surgery in rats (Roughan and Flecknell 2001, 2003) have reached the
point that they can be used more widely to assess pain in these species in a
variety of situations. It is also possible that some of the behaviors noted may
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50 Recognition and Alleviation of Pain in Laboratory Animals
be observed in other species: contraction of the abdominal muscles following
abdominal surgery is observed in rats and has also been reported in mice
(Wright-Williams et al. 2007) and rabbits (Leach et al. in press). Regardless of
the assessment technique, however, it is important that it be done by a team
that includes researchers, veterinarians, and animal care staff.
Pain recognition: Clinical signs and behavior
There are no generally accepted objective criteria for assessing the
degree of pain that an animal is experiencing. Species vary widely in their
response to pain, and often animals of the same species show different
responses to different types of pain. Box 3-1 presents a basic algorithm for
pain assessment that may be used until the development of species-specific
pain assessment methods. A team approach and cooperative spirit among all
interested parties (i.e., researchers, veterinarians, and animal care staff) will
benefit the welfare of the animal in pain.
BOX 3-1 Pain assessment protocol
The following approach can be helpful for assessing pain in particular
animal models:
Prepare a checklist of the examinations to be undertaken, allow space
for a general comment, and perhaps include an overall assessment tool (e.g., a
Visual Analog Scale (VAS) score sheet). Familiarize all staff who will be
involved in the assessment with this check list and any other assessment tools
that will be used. Whenever possible, the same staff member should conduct
each assessment of the same animal. Specific training must be provided for
new or inexperienced staff.
Begin by observing the animal without disturbing it. If the behavior of
the animal changes markedly in the presence of an observer (e.g., as is the
case with non-human primates, rabbits, and guinea pigs) it may be more
practical to assess postoperative or post-procedural behavior by setting up a
video camera or viewing panel.
Assess the animal's response to the observer (the technician who
routinely cares for the animal may be best able to assess this.)
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CHAPTER 3: RECOGNITION AND ASSESSMENT OF PAIN 51
Examine the animal and assess its response to gentle palpation or
handling of any presumed painful areas (e.g., the site of surgery, the site of a
lesion) when practicable.
Weigh the animal, record its food and water consumption if possible,
and examine the cage or pen for signs of normal or abnormal urination or
defecation.
Administer analgesic treatment if necessary, and repeat the assessment
outlined above 30-60 minutes after treatment to determine whether the dose
administered and the analgesic used have been effective. If uncertain as to
whether pain is present, assessing the response to an analgesic can be helpful.
Review these protocols regularly.
Remember that:
the signs described here can be caused by conditions other than pain
•
the signs may vary between animals of the same species, even after
•
the same procedure, and
• the signs will vary between different strains and breeds.
It is important that clinical evaluations and assessment protocols be
carried out by individuals with a detailed knowledge of the normal and
abnormal behavior and appearance of the species concerned. Further, the
effects of the observer on the behavior of the animal should be considered; for
example, some species, such as rabbits and guinea pigs, may remain immobile,
especially if the observer is an unfamiliar person. In these cases, it may be
necessary to observe the animal via a camera or viewing panel. When assessing
behavioral changes, it is often helpful to have a checklist that may incorporate
a grading scheme (see the scoring system developed by Morton and Griffiths in
1985). However, because different individuals often fail to agree on the score
that should be assigned (Beynen et al. 1987) it may be simpler to note the
presence or absence of a specific clinical sign. Changes in a score on
successive observations could indicate an improvement or deterioration in the
animal's condition. Many observations will not be specific indicators of pain,
but a structured examination is always helpful in monitoring an animal’s
progress during a study. Table 3-1 presents a number of behavioral signs usually
associated with pain.
Table 3-1 Behavioral signs of persistent pain
Sign Explanation
Guarding The animal alters its posture to avoid moving or causing
contact to a body part, or to avoid the handling of that
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52 Recognition and Alleviation of Pain in Laboratory Animals
body area.
Abnormal appearance Different species show different changes in their
external appearance, but obvious lack of grooming,
changed posture, and a changed profile of the body can
all be observed. In species capable of some degree of
facial expression, the normal expression may be altered
Altered behavior Behavior may be depressed; animals may remain
immobile, or reluctant to stand or move even when
disturbed. They may also exhibit restlessness (e.g., lying
down and getting up, shifting weight, circling, or pacing)
or disturbed sleeping patterns. Large animal species may
grunt, grind their teeth, flag their tail, stomp, or curl
their lips (especially sheep and goats). Primates in pain
often roll their eyes. Animals in pain may also show
altered social interactions with others in their group.
Vocalization An animal may vocalize when approached or handled or
when a specific body area is touched or palpated. It may
also vocalize when moving to avoid being handled.
Mutilation Animals may lick, bite, scratch, shake, or rub a painful
area
Sweating In species that sweat (horses), excessive sweating is
often associated with some types of pain (e.g., colic).
Inappetence Animals in pain frequently stop eating and drinking, or
markedly reduce their intake, resulting in rapid weight
loss.
Some analgesics, notably opioids, cause marked behavioral changes in
healthy, pain-free animals, which can confound attempts to assess pain
(Roughan and Flecknell 2000). Animals in pain will reduce their overall level of
activity, as observed in mice following surgery (Clark et al. 2004; Karas 2002;
Wright-Williams et al. 2007). Buprenorphine stimulates activity in normal mice
(Cowan et al. 1977; Hayes et al. 2000), so behavioral changes after the use of
this drug during surgery could be due to the provision of effective pain relief or
a non-specific drug effect. In contrast, NSAIDs have only very minor effects on
behavior in healthy, pain-free animals, so this problem is not significant with
the use of these analgesics (Roughan and Flecknell 2001; Wright-Williams et al.
2007).
It has been suggested that changes in heart rate, respiratory rate, and
blood pressure can be used to assess pain, but these clinical parameters are
often unreliable or nonspecific (e.g., similar changes may be observed in
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CHAPTER 3: RECOGNITION AND ASSESSMENT OF PAIN 53
stressed or distressed animals; NRC 2008). Consistent changes in these
parameters in animals expected to be in pain have not been demonstrated
(Cambridge et al. 2000; Holton et al. 1998; Price et al. 2003). Given the range
of factors (e.g., fear, excitement) that can alter heart and respiratory rate,
this is not surprising, as even handling can cause major changes in heart rate,
respiratory rate, and blood pressure. Recently, however, more sophisticated
analysis of heart rate variability has been of value as an adjunct to pain
assessment (Arras et al. 2007; Rietmann et al. 2004).
Pain assessment methods
As discussed above, methods for assessing pain in laboratory animals
remain highly subjective and are based largely on preconceived ideas about the
appearance and behavior of animals in response to pain. Attempts to apply the
Morton and Griffiths scoring scheme (Morton and Griffiths 1985) were largely
unsuccessful (Beynon et al. 1987), primarily because the variables selected for
inclusion were not fully identified, and the ratings (0-3) not sufficiently well
characterized (this scheme has proven much more successful in the
development of humane endpoints for studies presumed to involve distress
rather than pain; NRC 2008).
In addition to the lack of known effective pain assessment methods, it is
not uncommon for a study to include the administration of an analgesic without
any attempt to evaluate its effectiveness. For example, a recent survey of
pain control in laboratory animals in the United Kingdom found that, although
all the institutions in the survey used analgesics, almost none used methods of
pain assessment to confirm that the treatment was effective (Hawkins 2002).
Behavioral changes
Objective measures likely to indicate pain include changes in general
locomotor activity (e.g., guarding a specific area or avoiding weight-bearing on
an injured limb; Duncan et al. 1991; Flecknell and Liles 1991; Malavasi et al.
2006) and in food and water intake and body weight (Liles and Flecknell 1992,
1993a,b). These measures are also useful to assess analgesic drug efficacy,
although because they are retrospective, they cannot be used to modify
analgesic therapy for a particular animal. They are, however, effective as a
simple measure of postoperative recovery and as a means of adjusting future
analgesic regimens for similar animals undergoing similar surgical procedures.
The use of analgesics warrants certain cautions. The influence of
analgesics on body weight following surgery is not always easy to interpret. In
some studies, after an initial presumed beneficial effect, animals that had
undergone surgery and not received postoperative analgesics gained more
weight over a 2- to 3-day period than their counterparts under an analgesic
regime (Sharp et al. 2003). Further, significant behavioral signs of post-
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54 Recognition and Alleviation of Pain in Laboratory Animals
surgical pain in rodents may persist only 6 to 8 hours after some procedures
(Roughan and Flecknell 2004), so these results may be due to administration of
analgesics to animals that were not experiencing pain. In these circumstances
side effects such as sedation or nausea may be of much greater significance.
For more information on other behavioral measures the readers are referred to
Chapter 1, especially Box 1-4.
Behavioral assessment studies in rats, mice, and rabbits
Investigators have described specific behavioral changes following
abdominal surgery and ureteral calculosis in rats (Giamberardino et al. 1995;
Gonzalez et al. 2000; Roughan and Flecknell 2000). The abnormal behaviors
identified have been developed into a practicable pain assessment tool for use
in laboratory rats following abdominal surgery (Roughan and Flecknell 2002).
During the initial development of the scheme, rat behavior was evaluated both
before and after a mid-line laparotomy with appropriate untreated and
anesthetic and analgesic controls.
An initial study using buprenorphine as the analgesic was inconclusive
because of the marked effects of this opioid on normal behavior (Roughan and
Flecknell 2001). A subsequent study using carprofen and ketoprofen
successfully identified behaviors that differentiated rats that had (1)
undergone surgery from those that had simply been anesthetized and (2)
received analgesics following surgery from those that had not. These studies
required detailed analysis of considerable periods of videotaped behavior
including filming at night under red light. The utility of these behaviors was
further demonstrated in rats undergoing surgery as part of an unrelated
research project that entailed placing the animals in an observation cage for a
15-minute period and assessing the frequency of the pain-related behaviors.
Again, it proved possible to differentiate animals receiving analgesics from
untreated controls, and to demonstrate a dose-related effect of the NSAID,
meloxicam (Roughan and Flecknell 2003).
When experienced staff (animal technicians, research workers, and
veterinarians) viewed selected video recordings from these animals, they were
unable to correctly identify the treatment groups. However, after watching a
short recording illustrating the key behaviors, their ability to identify animals
that had or had not received analgesics greatly improved (Roughan and
Flecknell 2006). These studies suggest that key behaviors can be identified and
used to score pain following one type of surgical procedure in rats. In addition,
the studies underscore the importance of proper training of even experienced
personnel with the introducton of new techniques. It is not yet clear whether
behavioral changes in rats after various surgical procedures will differ greatly
in type or will be drawn from a common group of abnormal, pain-related
behaviors.
Recent studies in mice have indicated that they experience similar pain-
related changes in behavior after abdominal surgery (Wright-Williams et al.
2007) and that these behaviors might form the basis of a pain scoring scheme.
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CHAPTER 3: RECOGNITION AND ASSESSMENT OF PAIN 55
However, the rapid movement of mice makes observations less reliable. In
addition, the effects of the analgesics used in these studies were less
predictable than in rats as were the effects of opioids which affect behavior in
normal animals. These studies also found a major difference in the frequency
of pain-related behaviors in the two different strains of mice used (C3He and
C57Bl6). Other studies (Karas 2002) have shown changes in the frequency of
normal activity in mice following surgery, and it may be possible to develop a
scoring system based on a combination of changes in abnormal and normal
activity.
In some instances, changes in a specific locomotor pattern, or gait, can
be assessed objectively using a variety of techniques (Gabriel et al. 2007).
Measures such as using force plates and other means of assessing lim use and
gait patent have been used to evaluate the severity of arthritis in laboratory
and companion animals as well as the efficacy of analgesic therapy (Gabriel et
al. 2007; Hazewinkel et al. 2008). The linking of clinical signs to behavioral
alterations after administration of an analgesic facilitates pain assessment.
A small number of studies have attempted to assess post-surgical pain in
rabbits. Initial attempts to develop a behavior-based scheme failed because of
the animals’ reaction to the presence of an observer (Roughan et al. 2004), and
a similar study produced inconclusive results (Parga et al. 2003). More
recently, a detailed assessment of behavior before and after surgery, using
remotely operated cameras, revealed clearly identifiable abnormal behaviors
as well as changes in the frequency of normal behaviors. The effects of
analgesics were limited, and further work is required before clear
recommendations can be made about the usefulness of these behaviors (Leach
et al. in press).
A problem with all of these behavior-based schemes is that in many
instances the animals studied were anesthetized with regimens that resulted in
rapid recovery of consciousness (e.g., isoflurane or sevoflurane). When
recovery is delayed, or is associated with prolonged sedation, animals may fail
to express pain behavior and therefore scoring may not be reliable. The
scoring system may also be influenced by other factors, such as the animals’
fear and apprehension, or unexpected variations in behavior between different
strains (Wright-Williams et al. 2007). Nevertheless, detailed behavioral
observations are a step forward in developing a practical and useful pain
scoring system for use after surgery in laboratory animals. What is not yet
known is whether similar systems can be used to develop a means of identifying
and quantifying other types of pain in animals, including chronic pain (for a
discussion on the self-administration of analgesics and operant behavior see
Chapter 1).
Developing objective pain assessment tools: Companion animals
Initial attempts to score pain in companion animals used largely
subjective methods that were seriously flawed. Some studies, however,
demonstrated that behavioral assessments could be used to assess the effects
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56 Recognition and Alleviation of Pain in Laboratory Animals
of surgery and analgesia, as for example, the use of visual analogue scores to
assess pain following ovariohysterectomy in dogs (Lascelles et al. 1997) and
cats (Slingsby and Waterman-Pearson 1998). Additional scoring schemes for
use in dogs have since been developed (Firth and Haldane 1999; Holton et al.
2001), and numerous studies use VAS, Numerical Rating Systems, Simple
Descriptive Scores, or a mixture of all three approaches (Brodbelt et al. 1997;
Mathews et al. 2001). These different approaches highlight many of the
problems involved in developing pain assessment schemes (Holton et al. 1998),
some of which are presented here:
The assessment criteria are frequently highly subjective.
The study designs do not include untreated (surgery and no analgesia)
controls.
The study designs do not include anesthesia and analgesia (and no
surgery) control groups.
Only a single dosage is assessed rather than a range of doses.
Firth and Haldane (1999) videotaped dogs both before and after surgery
and after making detailed observations of their behavior, they identified
behaviors that were probable indicators of pain. In common with other
behavior-based scoring schemes, they hypothesized that behaviors that
appeared only after surgery, or which increased or decreased greatly in animals
following surgery, could be pain-related. Further, if administration of an
analgesic normalized these behavioral changes, this provided further evidence
that the changes were due to pain. The scheme set out by Firth and Haldane
has been developed further and recommended as a tool suitable for clinical use
(Gaynor and Muir 2002).
Holton and colleagues adopted a different approach (2001). This group
sought to identify descriptors of pain by consulting with experienced small
animal clinicians, and then used sophisticated analytical techniques to reduce
these descriptors to a set of words or phrases that could be developed into a
multi-dimensional pain scale. Unfortunately, validation in a placebo-
controlled, blinded study has yet to be completed.
It is important to note that the development of a pain score essentially
based on the opinion of clinician experts is almost certain to result in a self-
fulfilling scheme that will detect pain and predict which animals will receive
additional analgesics, since it will be used by clinicians whose opinion shaped
its development. This is a common problem in pain scoring of both animals and
humans and these schemes should be developed further and validated through
randomized, blind, placebo-controlled trials.
This proposition, however, poses significant ethical and practical
difficulties. Because most schemes include some behavioral assessments, and
because anesthetics and analgesics, notably opioids, can markedly change
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CHAPTER 3: RECOGNITION AND ASSESSMENT OF PAIN 57
behavior in normal, pain-free animals, lack of appropriate controls, i.e., post-
procedural animals that receive no anesthetic or analgesic, can make the
results highly questionable. The inclusion, however, of such control groups
may cause significant ethical dilemmas to researchers that undertake pain
assessment studies, most of which are carried out in veterinary schools.
Deliberately withholding analgesics in circumstances thought likely to result in
pain may be considered unacceptable by students taught that animals
experience pain and that analgesics should be administered. Studies of pain
with human participants require an intervention analgesia protocol so that
subjects assessed as experiencing pain above a predetermined level are
removed from the study and given an analgesic. This approach has been used
in a number of veterinary clinical studies (Grisneaux et al. 1999; Lascelles et
al. 1995).
Measurement of nociceptive responses11
A wide variety of methods apply to either momentary or more longer-
lasting noxious stimuli for research purposes (Hogan 2002; Le Bars et al. 2001).
Although these have limited application for assessing pain in other situations
(e.g., following surgery), they do provide insight into potential pain-related
behaviors and can help predict effective analgesic drug dose rates. Techniques
that measure momentary nociceptive responses involve the application of a
brief noxious stimulus, followed by quantification of the animals' response.
Administration of analgesics usually modifies this response, for example by
prolonging the latency of withdrawal of a limb or tail from the noxious
stimulus. In addition to their use in small laboratory animals, they have also
been applied to studies in larger species to assess analgesic efficacy and detect
the occurrence of hyperalgesia following injury (Dixon et al. 2002; KuKanich et
al. 2005; Ley and Waterman 1996; Pypendop et al. 2006; Slingsby et al. 2001;
Veissier et al. 2000; Welsh and Nolan 1995).
Although primarily used as a means of screening for potential analgesics
in drug discovery programs, the results of these tests have been used to
estimate dose rates of analgesics for clinical use in both large and small
animals. Such extrapolations, however, must be made with caution. It has
been shown that estimates of appropriate doses of buprenorphine based on tail
flick tests resulted in a recommended dose of 0.5 mg/kg in rats (Flecknell
1984), a dose 10 times higher than that proven to be effective using
11
The Committee acknowledges the publication of work pertinent to this section on both small
laboratory rodents and larger animal species. However, the subchapter is presented in an
abridged format in uniformity with the rest of the report. The Committee urges readers who
wish to delve more into this topic to begin with the references included and expand their
reading through them.
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58 Recognition and Alleviation of Pain in Laboratory Animals
postoperative pain scoring systems (Roughan and Flecknell 2004). Since high
doses of this agent can have undesirable side effects, it is important to
approach these extrapolations very carefully.
Although the results of these tests may not predict clinical efficacy, they
do illustrate the very wide variation in response between different strains of
rodents (Mogil et al. 1999; Morgan et al. 1999) and thus reinforce the
importance of developing pain scoring schemes. If appropriate pain scoring
schemes cannot be used, then dose rates are probably best estimated based on
the results of inflammatory pain models such as the late-phase formalin test
(Roughan and Flecknell 2002; Appendix 1 provides additional details).
Biological markers of nociceptor activation
Although biomarkers of nociceptor activation can only be used as
research tools, they can indicate whether a particular procedure could cause
pain. For example, the early gene product c-fos, (Coggeshall 2005) has been
used as a marker of nociceptor activity in a number of species (Lykkegaard et
al. 2005; Svendsen et al. 2007). Such assessments can only be made within a
short time after the animal is euthanized and so are not suitable for routine
clinical use.
As discussed in Chapter 2, nociceptor activation and some of the other
peripheral and central changes associated with pain and tissue damage result
in alterations of sensory thresholds, notably hyperalgesia and allodynia (i.e.,
the perception of previously non-noxious stimuli as noxious). These changes
have been used as indicators of both nociceptor activity and the efficacy of
analgesic therapy in both laboratory and clinical studies (Lascelles et al. 1997;
Whiteside et al. 2004). Although these methods essentially measure peripheral
changes, it is reasonable to assume that in conscious animals such changes
indicate that pain has been experienced and may still be present.
Brain activity imaging
Recent imaging studies have demonstrated that exposure to noxious
stimuli activates a range of cortical and subcortical areas. These areas
comprise both primary somatosensory cortex and areas associated with the
affective component of pain in humans (Hess et al. 2007; see also Box 1-3).
Although such activation does not demonstrate awareness of pain in animals, it
clearly indicates activation of the cortical areas considered necessary for the
affective component of pain. The use of imaging offers a novel approach for
detecting central processing of nociceptive information in animals and this may
enable a more objective assessment of the potential for particular procedures
or conditions to cause pain.
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CHAPTER 3: RECOGNITION AND ASSESSMENT OF PAIN 59
Pain assessment: Species-specific clinical signs
There is a remarkable lack of validated behavioral signs of pain in many
species (Viñuela-Fernández et al. 2007). The following sections present a
number of species-specific clinical manifestations based on expert clinical
opinion and best practices. Although the signs described typically accompany
or indicate pain, many are not specific to pain and may occur as general signs
of ill health or as responses to stress or distress (readers are encouraged to
consult the ethograms and tables with species-specific clinical signs indicating
pain, distress, or discomfort included in the Appendix of the NRC report
Recognition and Alleviation of Distress in Laboratory Animals 2008).
Nonhuman primates
Nonhuman primates show remarkably little reaction to surgical
procedures or to injury, especially in the presence of humans, and might look
well until they are gravely ill or in severe pain. Viewing an animal from a
distance or by video can aid in detecting subtle clinical changes. Loud and
persistent vocalization is an occasional but unreliable expression of pain as it is
more likely to signify alarm or anger. Therefore, it should be recognized that a
nonhuman primate that appears sick is likely to be critically ill and might
require rapid attention.
A nonhuman primate in pain has a general appearance of misery and
dejection. It might huddle in a crouched posture with its arms across its chest
and its head forward with a "sad" facial expression or a grimace and glassy
eyes. It might moan or scream, avoid its companions, and stop grooming. A
monkey in pain can also attract altered attention from its cagemates varying
from a lack of social grooming to attack. The animal may show acute
abdominal pain through facial contortions, clenching of teeth, restlessness, and
shaking accompanied by grunts and moans. Head pain may be manifest by
head pressing against the enclosure surface. Self-directed injurious behavior
may be a sign of more intense pain. Primates in pain usually refuse food and
water. If an animal is well socialized (e.g., trained to perform tasks as part of
a research protocol), changes in response to familiar personnel or in willingness
to cooperate may indicate pain.
Dogs
Dogs in pain generally appear less alert and quieter than normal
although small breeds are generally more reactive to environmental changes
than large dogs. Dogs in pain may move stiffly and unwilling to move, and if in
in severe pain may lie still or adopt an abnormal posture to minimize
discomfort. In less severe pain, dogs can appear restless and more alert.
Other apparent potential changes include inappetence, shivering, and
increased respiration with panting. Dogs in pain may bite, scratch, or guard
painful regions and if handled, may be abnormally apprehensive or aggressive.
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62 Recognition and Alleviation of Pain in Laboratory Animals
abnormal behaviors associated with pain. Lambs castrated surgically without
anesthesia remain largely immobile for prolonged periods but the endocrine
stress response produced by this method is even greater than that produced by
rubber ring occlusion (Lester et al. 1991). Because the types of behaviors
observed in lambs undergoing these different types of procedure varied, it was
not possible to use behavior alone to rank the degree of pain. However, the
behavioral responses could be used to compare methods of reducing the pain
associated with each procedure (Molony et al 2002).
Horses
Horses in acute pain show reluctance to be handled, and their other
responses are varied (Ashley et al. 2005; Driessen and Zarucco 2007): periods of
restlessness, interrupted feeding with food held in the mouth uneaten, anxious
appearance with dilated pupils and glassy eyes, increased respiration and pulse
rate with flared nostrils, profuse sweating, and a rigid stance. Horses in pain
also grind their teeth, switch their tails, or play with their water bucket. In
prolonged pain, their behavior might change from restlessness to depression
with head lowered. In pain associated with skeletal damage, there is
reluctance to move; limbs might be held in unusual positions (e.g., stand
“parked” with the weight on the hind feet and one front foot “pointed” ahead
of the other), and the head and neck in a fixed position. Horses with
abdominal or thoracic pain may look at, bite, or kick their abdomen; get up
and lie down frequently; walk in circles; stand “parked” with elbows adducted;
and sweat, roll, and injure themselves as a result of these activities, with
bruising especially around the eyes.
Cattle
Cattle in pain often appear dull and depressed, hold their heads low,
and show little interest in their surroundings. Their overall activity may be
reduced (Hudson et al. 2008). Other observable changes include inappetence,
weight loss, grunting and grindig of teeth, and, in milking cows, decreased milk
yield (Hernandez et al. 2002, 2005). Severe pain often results in rapid, shallow
respiration. On handling, they may react violently or adopt a rigid posture
designed to immobilize the painful region. Localized pain may be associated
with persistent licking or kicking at the offending area and, when the pain is
severe, bellowing. Generally, signs of abdominal pain are similar to those in
horses, but less marked. Rigid posture can lead to a lack of grooming because
of an unwillingness to turn the neck. With acute abdominal conditions, such as
intestinal strangulation, cattle adopt a characteristic stance with one hind foot
placed directly in front of the other.
The behavior of calves after dehorning and castration without anesthesia
has been described in detail (Molony et al. 1995; Stafford and Mellor 2005) and
includes decreased rumination and feeding and an increased incidence of ear
flicking, tail flicking, and head shaking. After castration using a rubber ring,
calves showed restlessness, foot stamping/kicking, stretching, and adjustments
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CHAPTER 3: RECOGNITION AND ASSESSMENT OF PAIN 63
of posture (“easing quarter”). In contrast, after crushing (Burdizzo) or surgical
castration the most marked behavioral change was statue standing (Molony et
al. 1995).
Sheep and Goats
Signs of pain in sheep and goats are generally similar to those in cattle,
but sheep, in particular, tolerate severe injury without overt signs of pain or
distress. There is a general reluctance to move along with changes in posture,
movement and in facial expression. Pain can also cause cessation of
rumination, eating, and drinking, and increased curling of the lips; but, as in
other species, these are not reliable indicators of pain. Goats are more likely
than cattle to vocalize in response to pain. They may also grind their teeth,
have rapid and shallow breathing, change posture frequently, and appear
agitated (foot stamping). Dairy goats will quickly decrease production and lose
body weight and general body condition. After castration or tail docking,
lambs show very characteristic signs of pain by standing and lying repeatedly,
wagging their tails, occasionally bleating, and displaying neck extension, dorsal
lip curling, kicking, rolling, and hyperventilation (Molony et al. 2002).
Pigs
Pigs in pain might show changes in their overall demeanor, social
behavior, gait, and posture and an absence of bed making. They may become
apathetic and unwilling to move and may hide in bedding if possible. Pigs
normally squeal and attempt to escape when handled, and pain can accentuate
these reactions or cause adults to become aggressive. Squealing is also
characteristic when painful areas are palpated. More moderate pain may
simply reduce activity levels and make the animal less responsive to familiar
handlers and reluctant to feed or drink (Harvey-Clark et al. 2000; Malavasi et
al. 2006).
Birds and poultry
Birds in pain show escape reactions, vocalization, and excessive
movement. Small species struggle less and emit fewer distress calls than large
species. Head movements increase in extent and frequency. There may also
be an increase in heart and respiratory rates. Birds with chronic pain may
exhibit a passive immobility characterized by a crouched posture with closed or
partially closed eyes and head drawn toward the body and may also become
inappetent and inactive with a drooping, miserable appearance, holding their
wings flat against the body and their neck retracted. There may be reduced
perching or birds may remain at the bottom of the cage. When a bird is
handled, its escape reaction may be replaced by immobility. Birds with limb
pain avoid use of the affected limb and refrain from extension.
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64 Recognition and Alleviation of Pain in Laboratory Animals
Reptiles
Acute pain in reptiles is characterized by flinching and muscle
contractions. There might be aversive movements away from the unpleasant
stimulus and attempts to bite. Chronic and persistent pain may be associated
with inappetence, lethargy, and weight loss, although it is difficult to associate
any of these signs of lack of well-being specifically with pain.
Fish
It is difficult to determine the nature of the response to pain in fish or
whether their experience is similar to that observed in mammals (Arena and
Richardson 1990; Rose 2002; Sneddon 2006; see Chapter 1). Although there
have been few species-specific studies, there is evidence that fish exhibit a
pronounced initial response to injuries or to contact with nociceptive stimuli or
chemical algesics (Sneddon 2003; Sneddon et al. 2003a, b; Reilly et al. 2008;
Ashley et al. 2009) but their response to chronic stimuli has not been
characterized. Generally, fish react to noxious stimuli (such as puncture with a
hypodermic needle) with strong muscular movements, and when exposed to a
noxious environment (such as an acidic solution) show abnormal swimming
behavior, attempts to jump from the water, and more rapid opercular
movements. Such effects indicate some, perhaps considerable, distress, but it
is not possible to describe the distress unequivocally as pain-induced.
Recent research has identified nociceptors in fish (Ashley et al. 2006,
2007; Sneddon 2002; Sneddon et al.2003a) that are physiologically similar to
mammalian nociceptors. In vivo administration of a noxious stimulus resulted
in aberrant behaviors (rocking on the substrate and rubbing of the affected
area) and adverse changes in physiology in rainbow trout over a period of 3 to 6
hours (Sneddon et al. 2003a,b); morphine reduced the incidence of these
behaviors (Sneddon 2003; Sneddon et al. 2003b). Recent research has also
shown that, after a one-time subcutaneous injection of 1% acetic acid to the
lower and opper frontal lip, trout do not show appropriate neophobic or anti-
predator behaviours when compared to behavioral impairments associated with
pain (Ashley et al. 2009; idem.). Goldfish given electric shock display agitated
swimming behavior but the threshold for this response increases if morphine is
injected, while naloxone blocks the morphine effect (Jansen and Greene 1970).
Work by Ehrensing and colleagues (1982) showed that the endogenous opioid
antagonist MIF-1 downregulates sensitivity to opioids in goldfish, which then do
not show an escape response to electric shock.
Studies have shown that goldfish are able to learn to avoid noxious,
potentially painful stimuli such as electric shock (Portavella et al. 2002, 2004).
Learned avoidance of a stimulus associated with a noxious experience has also
been observed in other fish species including common carp and pike (Esox
lucius), which avoided hooks in angling trials (Beukema 1970a, b; Overmier and
Hollis 1983, 1990).
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CHAPTER 3: RECOGNITION AND ASSESSMENT OF PAIN 65
Amphibians
Amphibian species such as anurans (frogs and toads) and urodeles
(salamanders) are commonly used in laboratory animal research settings
(Schaeffer 1997), but there is no objective means to assess the presence and
severity of pain in amphibians, especially since they do not exhibit any facial
expression (Hadfield and Whitaker 2005). Some exotic animal clinicians use
nonspecific clinical signs such as decrease in avoidance movement (e.g., when
approached by a handler) or decrease in appetite as indicators of pain in these
animals. Research studies have shown that amphibians are able and motivated
to learn to avoid noxious stimuli (Strickler-Shaw and Taylor 1991).
Conclusions and recommendations
Further studies to develop robust, reliable, broadly applicable pain
assessment tools are required. The general assumption is that the magnitude
of the clinical signs and behavioral changes observed correlates closely with
the intensity of pain. The extend to which these behavior-based assessments
reflect the affective component of pain (see Chapter 1) is uncertain and
requires an improved understanding of the nature of pain, consciousness, and
affective state in animals (see Chapter 1). Further, the lack of overlap
between the assessment techniques used by veterinarians, pain researchers
(Appendix 1), and psychologists (Box 1-4) is a notable impediment to progress
toward a broadly shared understanding.
In conclusion, the committee offers the following observations and
recommendations:
1. Pain in animals is difficult to assess and greatly depends on the
combination of a structured clinical examination with a good knowledge of
the normal appearance and behavior of the animals involved.
2. Observing animals’ response to analgesic treatment can help refine
clinical assessment schemes.
3. As more objective pain assessment schemes are developed, these should
be adopted. The paucity of information on species other than farm animals,
rats, and mice is detrimental to the animals’ welfare and well-being as well
as the quality of scientific research.
4. Responses of animals in analgesic drug tests and in models of pain can
help identify specific behaviors for use in assessment schemes. Results of
studies using these models can also identify sources of variation, and factors
that may influence pain intensity and analgesic efficacy.
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66 Recognition and Alleviation of Pain in Laboratory Animals
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