pre-clinical pain research tools Flashcards
why do we need pain research tools
test analgesic efficacy
understand pain mechanisms
identifying predictors and biomarkers of pain
in vitro vs in vivo research
vitro = isolate individual components, highly controlled, cell culture etc vivo = examine whole systems = less control but greater relevance for translation
what are reflexive tests (pain in animals) and what are they good for
activate nociceptors at site of testing and trigger localised stereotyped motor responses
goof for peripheral and spinal mechanisms
what are non-reflexive tests, what do they measure and what are they good for
spontaneous pain behaviour (eg paw licking after injection), analgesic self-admin, avoidance, quality of life
for cortical and descending modulatory mechanisms + clinical outcomes/disability
examples of reflexive tests for thermal stimulus
tail flick = spinal reflex, mod by brainstem
hot plate = spinal + integration for which paw to lick
hargreaves = hindpaw = hot plate + control paw
examples of reflexive tests for mechanical stimulus
von frey filaments = bend at ceratin pressure
cutaneous mechanical allodynia in neuropathic and inflammatory pain models looking at withdrawal threshold
or mechanical pressure for joint or muscle for deep somatic pain
what is the stimulus response curve for pain
describes that reflexive tests can be dosed
what are the key principles for basing animal pain models
- understanding clinical presentation and pathology
- behavioural measures that assess issues for particular disease
what is the acute post-surgical pain model
incision for superficial + deep-tissue injury
test mechanical allodynia (von frey)
guarding behaviour
how do we induce inflammatory pain in animals
what does it do to trp 1
what is the overall effect
- injecting irritants like capsaicin
- activated trpv1 containing polymodal nociceptors -> neurogenic inflammation + pain
- thermal + mechanical hyperalgesia (aD, C + silent nocicpetor sensitisation) and mechanical AB figure allodynia in surrounding areas (central sensitisation)
how do we study acute to chronic inflam pain and what does this induce
carrageenan injection
induces hyperalgesia + behvavioural + functional
model for sprain, strains, myositis
how do we study chronic pain and what does this induce
complete freunds adjuvant
induces hyperalgesia + behavioural and functional
models chronic inflam disorders eg rheumatoid arthritis
how do you induce neuropathic pain in animals
spinal cord injury
ligate or transect peripheral nerves
what a cronic constriction injury
constrict of sciatic nerve using chromic gut sutures
following surgery, measuring effect on von frey, to measure mechanical allodynia + latency to thermal stimuli for hyperalgesia
what is genetic + pharmacological modification + eg
modify receptors that are associated with pain
eg toll like receptor 4 = innat immunce receptor for mictobe + damage detection
KO TLR4 gene
