18.06.2015
Suzanne Ledahl
Attending Veterinarian, UiB
 Ethical reasons (KJS Anand – pain and its effects in the human neonate and foetus, 1987)
 Justice: if animals are models for human pain, we have
to assume they feel pain and treat it accordingly- you
can’t have it both ways! The model and the modelled
must be treated the same way to get quality of data
 Legal reasons (animal research highly regulated)
 Social/ economic: legislation/ funding guided by
public perception
1
18.06.2015
 Medical/ Scientific:
 hypothalamic- pituitary- adrenal axis (stress response, fight
or flight)
 renin-angiotensin-aldosterone system (preserve sodium,
increase circulation volume to prepare for bloodloss),
 red apetite
 immunosupression
 catabolism
 cachexia
 inadeq sleep
 retarded convalesecence
 poor science
 Parameter most frequently in clinical assessments of laboratory
animals
 Change in bodyweight does not always directly correlate to
distress/pain
Cancer (tumor may grow large)
Ascites
Pregnancy/ young animals
 Body weight analysis is retrospective and non-specific
 Rate of loss (or lack of gain) may be as important as absolute change
 How frequently should animals be weighed?
What is a reasonable comparison?
Untreated control? Retrospective control? Animals’ pre- procedure
weight?
2
18.06.2015
 Parameter most frequently in clinical assessments of laboratory
animals
 Change in bodyweight does not always directly correlate to
distress/pain
Cancer (tumor may grow large)
Ascites
Pregnancy/ young animals
 Body weight analysis is retrospective and non-specific
 Rate of loss (or lack of gain) may be as important as absolute change
 How frequently should animals be weighed?
What is a reasonable comparison?
Untreated control? Retrospective control? Animals’ pre- procedure
weight?
3
18.06.2015
 Rather than rely only on clinical impression and body
weight a range of clinical signs scored
 Overall score indicates likelihood of suffering
 Required for most FOTS applications
 Objective parameters important
 Subjective
Study endpoints scoresheet project no XXXX
Study endpoints are:
The procedure will be on the back of the rats so no interference with feeding or
drinking will be experienced. Infections in the area of the surgical wound, more
than 10% loss in body weight, ruffled fur and abnormal movement/ immobility
will be considered study endpoints.
When any animal reaches level 5, the animal will be euthanized.
Rat ID no
0
(none)
1
2
3
4
5
(severe)
Infection in
surgical
wound area
Loss of
weight >
10%
Abnormal
movement/
immobility
Ruffled fur
4
18.06.2015
 Objective
Arras et al. (2007). BMC Veterinary Research, 3:16 doi:10.1186/1746-6148-3-16.
 Objective
Scoresheet
0
1
Activity
Animal active and
inquisitive
Animal active,
but will not
come to greet
Unkempt
Fur
Normal
Pain
normal
Rapid
breathing
Facial grimace
score
normal
Reduced appetite
Reduced thirst
Reduced weight
Infection/ wound
normal
normal
stable
none
Movement
Neurological
symptoms
Tumor size
Blood/ urine
parameter
Eyes (nude strains)
2
3
Animal moves, but
quickly resettles
Animal only moves
when provoked
Dirty inguinal area/
black around eyes or
nostrils
1 of following
symptoms:
Hunced up position,
writhing, press,
twitch, stagger or
back arching
Occasional spikes
1 symptom on
grimace scale
2 symptoms on
grimace scale
3 symptoms on
grimace scale
-3-5%
-3-5%
-3-5%
Broken skin/scab
-6-10%
-6-10%
-6-10%
Weaping wound
Equal use of all
limbs
-1-2%
-1-2%
-1-2%
Skin is red,
swollen or
warm, but
intact
Foot held off
ground at rest
Limping, but placed
foot down
normal
Head tilt
Unsteady gait
Limping, does not
place foot on
ground at walk
Walks to one side
Falls over/ circling
2 or more of
following:
Hunced up
position,
writhing, press,
twitch, stagger or
back arching
4
Score/ Score/ Score/ Score/
date
date
date
date
Animal will not
move upon
provocation
Marked spikes/
soiled coat
Any of symptoms:
Hunced up
position,
writhing, press,
twitch, stagger or
back arching
despite analgesic
treatement
4 or more
symptoms on
grimace scale
-11-15%
-11-15%
-11-15%
Multiple wounds
Lame on multiple
legs
Paraplegia
5
18.06.2015
 Behavioural changes – know what is normal/
abnormal so you can detect pain/ distress even if not a
registered parameter on your scoresheet
 Firstly- you have to recognize the ”normal” rodent:
 Inquisitive
 Clear eyes
 Clean, groomed fur
 Nest in the cage
 Faeces and urine in cage
 Foraging
 Drinking
 Sleeping
 Natural bahviours: digging, rearing, climbing
6
18.06.2015
 Firstly- you have to recognize the ”normal” rodent:
 Inquisitive
 Clear eyes
 Clean, groomed fur
 Nest in the cage
 Faeces and urine in cage
 Foraging
 Drinking
 Sleeping
 Natural bahviours: digging, rearing, climbing
7
18.06.2015
 Firstly- you have to recognize the ”normal” rodent:
 Inquisitive
 Clear eyes
 Clean, groomed fur
 Nest in the cage
 Faeces and urine in cage
 Foraging
 Drinking
 Sleeping
 Natural bahviours: digging, rearing, climbing
8
18.06.2015
 Does not come to greet when open cage, may not
attempt to hide
 Does not groom itself or cage-mates (may be soiled in
the rear end)
 Does not eat or drink as normal (can be measured by
weighing food and/or water bottle- also assessed
visually by lack of faeces and urine in cage)
 Does not build nest (nesting material left unused)
9
18.06.2015
 However behaviours have been identified for only a very
few procedures in small no. of species (eg visceral pain)
 Time-consuming to develop & implement:
1.
2.
3.
Establish which behaviours indicate pain following a
procedure – Often requires >30mins of training1
Pain behaviours vary markedly between procedures
Accuracy is still only about 80%
10
18.06.2015
 Animal’s ability to cope with pain is individual
 Some rats are active when in pain- they explore the cage to
find out “why it hurts”
 Animals exhibit less signs of pain in presence of male
technician
11
18.06.2015
12
18.06.2015
13
18.06.2015
14
18.06.2015
15
18.06.2015
16
18.06.2015
17
18.06.2015
18
18.06.2015
19
18.06.2015
20
18.06.2015
21
18.06.2015
22
18.06.2015
23
18.06.2015
24