Midterm 2 Flashcards
what is ectopic firing?
fires all by itself to no apparent stimulus (whats happening to diabetic rat)
what is the role of glial cells?
Not electrically excitable like neurons, but they can be activated and they have receptors and transfer NT
what is microgliosis?
when they get activated and get angry
- Caused by injury in periphery
what are microglia?
function is immune surveillance
what is the function of astrocytes?
blood-brain barrier, neural support
what is an advantage of subjective/objective measures?
subjective: less constraint
objective: more reliable, tighter data
what is a cold pressor test?
The immersion of hand or elbow in cold water (~4C)
- Eventually the limb gets ischemic (low blood supply), which hurts
what is pressure algometry?
press down on a body part and machine keeps track of how much force is exerted
- Keep pressing until person says stop
explain the pain threshold and tolerance study (how many seconds)
pain threshold achieved at 25 sec and pain tolerance was achieved at 80 sec
- Tolerance: raise heat until person says to stop
- Threshold: say “now” when warm becomes painfully hot (threshold is temperature)
what is time a proxy (substitute) for?
It’s an easy way to measure the temperature that researchers think is painful
what is the human heat pain threshold?
43-46 degrees C
- Maybe hypertensives have a slightly lower threshold than control
why do we need to measure something other than threshold and tolerance?
Threshold and tolerance don’t tell you about clinical pain (it’s something we can measure, but not what we want to study)
- Could also be measuring people’s willpower
- Problem with threshold: its very subtle
what is the visual analog scale and why is it better than NRS?
no numbers, but on a spectrum
- Some people say a low number bc they want to make their healthcare provider feel like their treatment worked – they’ll memorize the number and choose a lower one later
what is the faces scale?
used for kids snce they have a hard time understanding descriptors
- Problem: the zero face is smiling (no pain doesn’t mean you’re smiling)
- Should start at neutral
- Another problem: when?
describe the use of the double VAS
Top: intensity
Bottom: unpleasantness
what is the most common pain rating on a scale?
11
- They don’t understand what researchers are asking – it’s far too common
what is causalgia?
type of neuropathic pain after traumatic injury
explain how much things hurt, from most to least (Melzack)
MOST:
- causalgia
- digital amputation
- childbirth
LEAST:
- sprained ankle
explain the FLACC scale for babies
Face
Legs
Activity
Cry
Consolability
who came up with a facial action coding system for pain?
Paul Ekman
what are pain descriptors?
Idea that you can define pain by the words that people use to describe it
explain Ron melzack’s pain descriptors by intensity
Came up with collected adjectives that people use to describe pain (divided into categories)
- Sensory: Temporal, spatial, punctate, incisive (cutting), constrictive (squeezing), traction, thermal, brightness
- Top: ones that were thought to be least intense of the category / bottom: most intense in category
explain the McGill pain questionnaire
- 20 qualitative questions
- PPI: present pain index
- 6 point verbal rating scale
- You pick the one that most describes your pain
- Idea: different types of pain would feature different types of descriptors
- Doesn’t work that well, except with one exception: inflammatory pain is more dull aching, whereas neuropathic pain is more sharp shooting axis
explain the MPQ short form questionnaire
- Instead of picking descriptors, you’re given descriptors
- Takes less time to fill out
- Advantage: shorter appointment times
explain the DN4 neuropathic pain questionnaire
- Allows clinicians to see if patients have neuropathic pain or not
- 4 questions, 10 points
- Yes to every question: 10 / no: 0
- 0-3: not neuropathic
- 4-7: probably
- 8-10 definitely have neuropathic
what is Hypoesthesia?
less feeling of
what is the Oswestry Disability Index?
- Asks how well your painkillers are working
- Mostly about how disabled are you
what is pain catastrophizing?
psychological concept that is an amalgamation of rumination, magnification, and helplessness
- Rumination + Magnification + Helplessness
- predicts who will get chronic pain and what their prognosis will be
what is the WOMAC questionnaire?
- Developed specifically for arthritis pain and arthritis in general
- Measures different contexts
- Section c: measure of disability
- Developed by western and mcmaster
what is quantitative sensory testing (QST)?
- Two ways – bedside examination + quantitative sensory testing
- Less controlled but can be done at the bedside in a clinical context (pinprick, metallic rollers)
- Very precise equipment, very precise instructions
- Use of psychophysics: series of methods of giving a bunch of different intensities of a stimulus to see where the threshold is
what is skin temperature?
32 degrees
what were the Different baseline heat thresholds in QST and heat hyperalgesia study?
42.1-44.5
explain the QST and mechanical allodynia study
- Data from 1 patient
- QST with: cotton whisp, Q tip, and brush
- Dynamic mechanical allodynia
- Left: forces that 3 items exuded
- Right hand: non noxious
- Left hand (painful hand): much more noxious
- You would think that the noxious stimuli would be more noxious compared to others ones, but they’re about the same
explain the QST the german way (PHN I and II)
-Determined that there are 2 types of PHN, gain of function and loss of function and they respond to QST procedures in diff
ways
PHN I:
- heat hyperalgesia
- pinprick hyperalgesia
- dynamic mechanical allodynia
- static hyperalgesia to blunt pressure
PHN II:
- cold/warm hypoesthesia
- tactile hypoesthesia
- pinprick hypoalgesia
- static hypoalgesia to blunt pressure
explain electrical, chemical, and mechanical pain testing in muscles
- Chemical: infuse chemicals into patients
- Electrical: stimulate muscles directly to get pain ratings
- Mechanically: pressing really hard with a probe (stimulate muscle and skin)
- A lot more invasive than regular QST
what are biomarkers?
measure with a machine
what is the original biomarker?
tissue damage
- Thought that the amount of pain should follow the size of the wound, but that does not work
what are neural biomarkers of pain?
EEG, microneurography (direct measurement of c fibers), imaging (controversial – some ppl think its good and others don’t)
what are chemical biomarkers of pain?
substance p, beta endorphin, nerve growth factor (all others don’t work but this one is still on the fence)
what are molecular biomarkers?
DNA, mRNA
- Why are these problematic?
- DNA variants: DNA doesn’t change no matter what happens
- mRNA: can have more or less expression of that gene – mRNA expressions differ in every tissue, which we don’t have access to unless mRNA levels in the blood turn out to be useful
what are cardiovascular biomarkers?
- heart rate
- blood pressure
- heart rate variability
what are stress-related biomarkers?
- cortisol (etc.)
- galvanic skin response
Can fMRI be Used as a Biomarker of Pain?
True in small sample, false in large sample
explain Hypnotic vs physically induced vs imagined pain
There’s a lot of overlap, even when there wasn’t pain
- If your brain is active in pain matrix, that might not mean pain
why use animals?
- can conduct causation experiments
- can stimulate/lesion any tissue
- can assay, record from, or extract any tissue
- can give unapproved drugs
- can alter gene expression (temporarily or permanently)
- can turn particular types of neurons in
particular locations on and off at will - can control pre-exposures
- cheaper, faster, less highly regulated
- no malingering, no stoicism/machismo,
- no demand characteristics
explain the consequentialist approach to animal experiment ethics
add up costs and benefits and come to a conclusion
explain the deontological approach to animal experiment ethics
there are things that we just shouldn’t do
explain the trends of Algesiometry in Rodents
- test with chemical, electrical, heat, cold, mechanical, spontaenous pain
- Mechanical testing has increased over time, and everything else is on a lower level
- Why? Mechanical hypersensitivity (allodynia and hyperalgesia) is a bigger problem than heat hypersensitivity
- heat testing has gone down
- electrical is never done at all bc animals dont get exposed to electric shock
what are challenges to the use of animals?
- they’re the “wrong” species
- they don’t talk
- they’re prey
- they’re a lot tougher than we are
- ethical issues
explain the hot plate test
Made out of ceramic and heated to a particular temperature
- Measure amount of time it takes for the animal to shake/lick paw (they don’t jump off right away)
- Measuring acute heat pain (the pain will only be there for a sec or two until the rat decides to do something)
- Why they choose to lick specific paw is unclear
difference between tail flick test and hot plate test
- Tail flick test is a reflex
- Hot plate test is a CONSCIOUS decision to do something
explain Hargreaves’ test
- Radiant heat paw withdrawal test: how long it takes for mouse to hop away from heat lamp (Hargreaves response)
- Put heat on each paw separately
- Measuring thermal acute pain
explain the von frey filament test
Made to test mechanical sensation
- Set of fibers range from thick to thin
- Each fiber can only exert x amount of force
- Measuring animal’s threshold of annoyance instead of pain (maybe)
The vast majority of pain research is about:
hind paw skin pain
explain the Randall-Selitto Test
- Only works in rats; mice will not stand for being held this way
- Putting the rat’s foot between two pieces of plastic and increase the force
- At some point to rat squeaks or does something
- IITC: more modern and automated version
How do you infer pain in weight bearing tests?
unequal input on both sides (weight on one side more)
How do you infer pain in grip force tests?
if mouse is unable to hold on with the same amount of force as before
How do you infer pain in gait changes?
if they are favouring or guarding one side they will show a different gate pattern (indirect measure)
explain the writhing test (what do you inject)
Inject nasty chemicals that cause inflammation or activate nociceptors into body parts
- Most common: acetic acid - irritates muscle wall in viserca
- Mice will squash their belly on the ground (measure how many times and for how long)
- Measuring behavioural response over time
- More behaviours –> more pain
explain the formalin test
Injection of formalin (dilute formaldehyde) that starts fixing tissue and cause inflammation
- Early: lots of licking
- Quiescent: looks like it’s much better
- Late: start licking again for 60-90 mins
what are the Most common inflammatory substances?
- carrageenan
- complete Freund’s adjuvant
- zymosan
- mustard oil
explain tonic/chronic inflammatory assays
Effects will last days to weeks
- They don’t do anything (lick, shake, nothing)
What they do do:
- Inflammatory thermal hyperalgesia on hargreaver test
- Inflammatory mechanical allodynia on von frey test
- Inflammatory cold allodynia: put acetone on paw (it evaporates) causing a cooling sensation (painfully cold), leading animal to lick paw
explain surgical Chronic Neuropathic Assays
Interfering through primary afferent through the foot (because the foot is easiest to test to see of there are changes)
- Making an injury that causes partial damage to nerve supply in the foot
- Remember: neuropathic pain is most often caused by partial pain
- Only things to measure: Cold and mechanical allodynia, thermal hyperalgesia
explain complete denervation (which nerves are cut and why there can’t be pain)
cut sciatic nerve and saphenous nerve to accomplish this (produces axotonomy: they start biting off their toes)
- Score it by counting how many toes are left
- There can’t be any pain, because there’s no afferent input from foot to spinal cord
if complete denervation isn’t painful, why are mice biting off their foot?
Leading explanation: they don’t think it’s part of them anymore (animal model of phantom limb)
what is complete axtonomy?
amputation
how can you cause neuropathy?
- viruses
- drugs
- Cause dysfunction of nerves, or cutting/inflaming them
name nociplastic and neuropathic types of pain
- Nociplastic: fibromyalgia
- Neuropathic: diabetic neuropathy, post-herpetic neuralgia
what is vulvodynia?
nociplastic disorder whose main feature is allodynia of the vulva
- lots of yeast infections
explain vulvodynia studies in mice
Gave mice yeast infections and treated them with antifungal over and over
- Noticed that after 3 rounds, they were getting allodynia that stayed instead of resolving
- Produced a state of permanent allodynia in mice
- Took 3-5 months
- Better way to study vulvodynia, but it takes too long
name The Big Three Criticisms of the Status Quo
(1) The methods that we use are reflexes, but the problem has nothing to do with reflexes
(2) Pain is associated with a bunch of comorbidities – why aren’t we measuring them?
(3) Disconnect between epidemiology of clinical symptoms and what we measure in animals
what is the opposite of reflexes?
conditioning
explain the motivational conflict between pain and drinking (operant conditioning study)
- Inject carrageenan in cheek, gets inflamed
- Wants to drink sweet water for reward, but only way to get it is press cheek against a heated plate
- Carrageenan produces mechanical and heat allodynia
- Not a reflex, the animal is making a choice
Why is this complicated? Maybe the experiment changed something other than pain
explain the conditioned place preference to analgesia
Used clonidine or conotoxin (analgesics)
- Partition in middle
- Other floor: saline
- Animals will spend more time on analgesic side when they have the choice, since they weren’t in pain
- SNL produced pain
- Complicated, requires a bunch of training
name the differences in percentages of pain in reality vs research
96% have spontaneous pain
64% have mechanical hypersensitivity
38% have thermal hypersensitivity
- Percentage of paper research:
48%, 42%, 10%
why are we understudying spontaneous pain?
Not as convenient to study and we couldn’t come to a conclusion on how to measure it
what is the mouse grimace scale?
index of how much pain the mouse is in
which species have criteria for pain perception?
- Birds have all of them
- Amphibians and reptiles have some of them
- insects may feel pain
what are organismic/experiential factors?
organismic: factors inside your body that can affect pain
experiential: things that happen to you
why do Ratings go from 5-95 for exact same stimulus?
- People might be using scale differently
- Perceptual variation
__% of people that go in for a surgery get chronic post-surgical pain
7%
How many surgeries are preformed every year in Canada?
1 million
explain pain ratings from patients Immediately upon waking up from anesthesia
60+: Most common score
Average: 70
Nurses gave a small dose of morphine and came back every hour - what were the averages?
- Massive variability – some required 1-10
- Average: 4 doses
- Range: 2-83 micrograms per kilo of body weight
difference between trait and state
Traits: stable / states: malleable