4446 Clinical Signs of Pain and Disease in Laboratory Animals

Revision Date: 
July 8, 2015
Responsible Official: 
IACUC Chair
Responsible Office: 
Office of Animal Research Support (OARS)

Guideline Sections

4446.1 Background

4446.2 Assessment of Pain, Distress and Discomfort in Mammals

4446.3 Assessment of Disease in Mammals

4446.4 Pain and Disease in Amphibians and Fish

Many species can mask clinical signs of pain, distress and disease, and signs can vary by species (with individual variation as well).  Therefore, it is imperative to have an understanding of normal behavior for that species/animal and to closely observe for clinical signs and behaviors that may indicate pain or disease.  The descriptions below describe species-specific clinical manifestations of pain and/or disease, though it is important to keep in mind that many of these signs are nonspecific or may occur due to general ill health.  The presence of any of these clinical signs may be useful for determining pain categories and setting criteria for experimental and humane endpoints.  

The following is a list of clinical signs and behaviors that may indicate pain:

Rats and Mice*

Sign or Behavior

Comments

Abnormal posture

Hunched posture is a general sign of pain or disease

Behavior changes during handling

May be unusually aggressive or placid

Changes in activity/mobility

Decreased mobility may be localized to area of pain (e.g. limb) or may be generalized.  Rodents in pain generally have decreased activity, but increased activity may also be seen. Other abnormal behaviors include back-arching, belly-pressing, twitching, and staggering.

Changes in facial expression

Utilizing a grimace scale may be beneficial in identifying pain

Decreased body temperature

Animals that feel cold to the touch are likely severely hypothermic and may be moribund

Decreased food and/or water intake

May be associated with weight loss, dehydration, and decreased urine/fecal output.  Prolonged skin tent indicates dehydration.  Body condition scoring may be more useful than body weight in some circumstances1.

Decreased grooming, piloerection

Coat appears scruffy, hairs may be raised

Decreased nest-building

Particularly meaningful in mice, which have a strong drive to build nests

Decreased response to external stimulation

Attempts to escape when handled are normal in rodents unless well-habituated to handling – failure to exhibit this behavior may indicate pain or distress

Licking, scratching at painful site

May result in trauma or exacerbate lesion severity due to self-mutilation

Pale mucous membranes/extremities

Easiest to visualize by examining paws, tails, ears; can also look in mouth

Porphyrin (red pigment) staining around eyes, nose, paws, forelimbs

Generally pertains to rats

Separation from group

Mice & rats are social and normally rest in close proximity to one another during the day (are nocturnal)

Shallow and/or rapid respirations

Normal respiratory rate = 100-230 breaths per minute

Squinting of eyes

By itself this sign could indicate pain associated with ocular problem, but if combined with other signs, such as ear position, whisker change, nose bulge, it could also indicate an extra-ocular source of pain.

Teeth chattering, vocalization

 

*Although there is little information in the literature regarding specific signs of pain in other small rodents, use of the signs in the table above is recommended as a guideline for pain assessment; particularly: decreased activity, piloerection, ungroomed appearance, abnormal posture, and changes in respiration.   

Ground Squirrels

Sign or Behavior

Comments

Changes in activity/mobility

Looping the cage without stopping, sneezing

Decreased food and/or water intake

Reduced food and water intake is normal for pre-hibernation squirrels

Decreased grooming, piloerection

 

Quiet, less alert

 

Guinea Pigs & Hamsters

Sign or Behavior

Comments

Changes in activity/mobility

 

Decreased food and/or water intake

This may exacerbate gut stasis that can occur post-operatively or secondary to pain

Decreased grooming, piloerection

 

Hiding

 

Quiet, less alert

Normal guinea pigs stampede and squeal when startled, when attempts are made to handle them, or when strangers are in the room; however, guinea pigs also tend to freeze in the presence of an observer, which makes assessment of attitude difficult

Shallow and/or rapid respirations

Normal respiratory rate = ~40-100 breaths per minute at rest

Social behavior

May show less interest in play or social interactions

Rabbits

Sign or Behavior

Comments

Abnormal posture

With abdominal pain, may have arched back, contraction of the abdominal muscles, and abdominal pressing

Behavior changes during handling

May attempt to hide; reactions to handling may be exaggerated (e.g. rapid fits of locomotion); may vocalize if in acute pain

Changes in activity/mobility

Twitching, wincing, flinching may also be observed while at rest

Changes in facial expression

Utilizing a grimace scale may be beneficial in identifying pain

Decreased food and/or water intake

This may exacerbate gut stasis that can occur post-operatively or secondary to pain.  May present as scant and/or small fecal pellets.

Decreased grooming

 

Hiding

 

Localized licking, biting, scratching

May be associated with localized pain

Quiet, less alert

 

Shallow and/or rapid respirations; may also have slow, deep respirations with nasal flaring

Normal respiratory rate = 30-60 breaths per minute at rest

Teeth grinding

May occur but is not completely reliable as a behavioral indicator

Vocalization

 

Dogs

Sign or Behavior

Comments​

Abnormal posture or gait

 

Behavior changes during handling

May be unusually apprehensive or aggressive; may show less interest (e.g. decreased tail wagging) towards familiar handlers

Changes in activity/mobility

Dogs in pain may move stiffly or be unwilling to move.  If pain is less severe, the animal may be restless and more alert.  Localized pain to the limbs may cause limping or holding up the limb.

Decreased food and/or water intake

 

Localized licking, biting, scratching

May be associated with localized pain

Quiet, less alert

 

Shallow and/or rapid respirations

Normal respiratory rate = 10-35 breaths per minute at rest

Shivering

 

Social behavior

May show less interest in play or social interactions

Vocalization

Spontaneous barking is unlikely; more likely to whimper or howl; may growl without apparent provocation (note that lack of vocalization is not a reliable indicator of pain level)

Cats & Ferrets (If species-specific signs/behavior indicate the relevant species)   

Sign or Behavior

Comments​

Abnormal posture or gait

May crouch/hunch in response to abdominothoracic pain; may extend head/neck/body with thoracic pain; may stand or lie on its side with its back arched or walk with a stilted gait with abdominal or back pain

Behavior changes during handling

May be unusually aggressive or attempt to escape

Changes in activity/mobility

Localized pain to the limbs may cause limping or holding up the limb

Decreased food and/or water intake

 

General lack of well-being

Cats are less reactive to environmental changes compared to dogs; cats in severe or chronic pain look ungroomed and behave markedly differently from normal

Hiding

 

Localized licking

May be associated with localized pain

Quiet, less alert

 

Shallow and/or rapid respirations

Normal respiratory rate = 20-40 breaths per minute at rest

Social behavior

May show less interest in play or social interactions and/or may separate from the group

Vocalization

May cry, yowl, growl or hiss in response to handlers

Sheep and Goats

Sign or Behavior

Comments

Abnormal posture

May be holding head low; may change posture frequently

Behavior changes during handling

May stamp feet and otherwise appear agitated

Changes in activity/mobility

General reluctance to move

Decreased food and/or water intake

May be associated with decreased or cessation of rumen activity; weight loss may occur

Localized licking or kicking

May be associated with localized pain

Quiet, less alert

May appear dull and depressed, show little interest in surroundings

Shallow and/or rapid respirations

Normal respiratory rate =10-30 breaths per minute at rest

Teeth grinding

 

Vocalization

Especially goats

Pigs

Sign or Behavior

Comments

Behavior changes during handling

Squealing/attempting to escape may become more pronounced than usual; can become aggressive; may be less responsive to familiar handlers

Changes in activity/mobility

General reluctance to move; may be restless

Decreased food and/or water intake

 

Hiding

 

Quiet, less alert

 

Shallow and/or rapid respirations

Normal respiratory rate = 17-23 breaths per minute at rest

Social behavior

May show less interest in social interactions with humans and/or conspecifics

Teeth grinding

 

Vocalization

May become more pronounced

Birds

Sign or Behavior

Comments

Abnormal posture

Crouched posture with closed eyes and head drawn towards body in chronic states of pain; neck may be retracted; ruffled feathers or “puffed up” appearance

Behavior changes during handling

Escape reactions enhanced or dulled; small species struggle less and emit fewer distress calls than large species

Changes in activity/mobility

May show excessive movement; head movements increase in extent and frequency; immobility may occur in response to chronic pain; localized pain to a limb may cause decreased use or holding limb close to body; standing on one leg, shifting leg lameness, standing on metatarsus, or resting on sternum

Reduced perching

May be found at bottom of the cage

Shallow and/or rapid respirations

 

Vocalization

Decreased or abnormal vocalization

Specific clinical signs of disease are dependent upon the system affected, and may or may not be associated with pain.  The following list provides examples of clinical signs that may be seen when disease affects specific body systems.     

System

Clinical signs that may be observed

Respiratory

Altered respiratory depth, rate, and effort; pale or cyanotic mucous membranes, open-mouth breathing

Urinary

Increased or decreased urine production; increased water intake; dehydration; weight loss; penile prolapse;  urinary obstruction (enlarged bladder) secondary to fight wounds affecting genitalia in males

Gastrointestinal

Diarrhea or soft stool with or without blood; prolapsed rectum; weight loss; dehydration; (note: rodents cannot vomit)

Nervous

Depression/severe lethargy, seizures; autophagia; ataxia; paralysis

Cardiovascular

Increased respiratory rate; pale or cyanotic mucous membranes; lethargy; weight loss

Musculoskeletal

Lameness; swelling; biting/scratching at affected area; muscle atrophy if chronic

Immune

Nonspecific signs of illness due to secondary infection; enlarged lymph nodes; abscessation

Reproductive

Females: vaginal/uterine prolapse; discharge; difficulty giving birth

Males: penile/preputial trauma (due to fighting); penile prolapse

Integumentary

Ulceration (e.g. ulcerative dermatitis); fight wounds (usually found on the hind end and genitalia in males); pustules; abscesses; necrotic tissue; unkempt coat due to decreased grooming

Non-specific signs of illness

Unkempt coat; hunched posture; dehydration; decreased food/water intake; inactivity; decreased nest-building (mice); porphyrin staining around eyes, nose, etc. (rats) 

The topic of pain in reptiles, amphibians and fish is controversial; these species demonstrate avoidance behavior in response to noxious stimuli, but whether this is truly considered pain is widely debated.  Therefore, for these animals, a general assessment of health should be made if there are any concerns regarding potential pain, distress or disease.  The following list provides examples of clinical signs that may be seen in these animals.   

Reptiles

Sign or Behavior

Comments

Behavior changes during handling

May attempt to bite

Decreased food and/or water intake

May be associated with weight loss

Flinching and muscle contractions

 

Quiet, less alert

 

Amphibians

System

Clinical signs that may be observed​

Gastrointestinal

Increased or decreased defecation; regurgitation of stomach contents; decreased food intake

Integumentary

Changes in skin color, skin sloughing, white film on skin

Whole body

Weight gain or bloating; weight loss or thin body condition

Behavioral

buoyancy problems, floating on water’s surface, reluctant to dive, turning outward of front limbs, swimming with a whole body tilt, swimming upside down or in circle, lack of avoidance behavior (e.g. to handlers)

Fish

System

Clinical signs that may be observed

Gastrointestinal

Decreased food intake

Integumentary

Fin abnormalities; white film on scales; missing scales; skin/scale discoloration; ulceration; raised scales

Whole body

Enlarged abdomen/bloating

Ocular

Clouded eyes; protruding eyes

Behavioral

lethargy, swimming sideways, staying at the bottom of the tank, rubbing against surfaces, gasping at water’s surface; separation from others (schooling fish such as zebrafish); quick twisting swimming motion (“flashing”)

Contact Information

Subject

Contact​

Phone

Animal Health

Veterinary Clinical Services (VCS)

(203) 785-2501

Policy

Office of Animal Research Support (OARS)

(203) 785-5992

Revision History

5/16/07; 12/10/10; 9/12/12; 7/8/15

References

  1. Ullman-Cullere, M. H. and Foltz, C. J. (1999). Body condition scoring: a rapid and accurate method for assessing health status in mice. Lab Anim Sci. 49(3):319-23 
  2. Recognition and Alleviation of Pain in Laboratory Animals.  National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals.  Washington (DC): National Academies Press (US); 2009. 
  3. Suckow, MA, Stevens, KA, Wilson, RP.  2012.  The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents.  Academic Press: San Diego, CA. 
  4. AALAS reference directory
  5. Sotocinal, Susana G et al. “The Rat Grimace Scale: A Partially Automated Method for Quantifying Pain in the Laboratory Rat via Facial Expressions.” Molecular Pain 7 (2011): 55. PMC. Web. 7 July 2015.
  6. Leach MC, Klaus K, Miller AL, Scotto di Perrotolo M, Sotocinal SG, Flecknell PA (2012) The Assessment of Post-Vasectomy Pain in Mice Using Behaviour and the Mouse Grimace Scale. PLoS ONE 7(4): e35656. doi:10.1371/journal.pone.0035656
  7. Lab Anim (NY). 2015 Jun 19;44(7):259-60. doi:10.1038/laban.806.
  8. Using the facial grimace scale to evaluate rabbit wellness in post-procedural monitoring. Hampshire V1, Robertson S2.

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