Midterm 1 Flashcards
What is stress-induced analgesia?
When stress inhibits pain
Study:
- Similar wounds between soldiers and civilians
- The soldiers were much more likely to say there was a little pain vs the civilians who described more pain
- Civilians wanted narcotics more
- Only difference: context
What were the confounds in the study of pain and narcotics between soldiers and civilians?
Confounds: soldiers are young and civilians are middle-aged, levels of stress differ
Explain the osteoarthritis example
MAIN POINT: Injury is not the thing that causes the pain in everyone, only some people
Every participant had knee OA that a rheumatologist diagnosed
- Most didn’t have pain in their knee, even though they all had the injury
- You can have OA but not knee pain and you can have knee pain but not OA
- OA sort of causes this pain
Pain is the #1 _____
- reason to seek healthcare
- concern of patients with chronic disease
What are the top 10 presenting complaints at doctor visits?
Cough*
Back pain*
Abdominal pain*
Sore throat
Dermatitis
Fever*
Headache*
Leg pain
Respiratory
Fatigue
What are the most common and least common pain events?
Most common:
- scratched skin (95.2%)
- paper cut (95.2%)
- pinched skin (94.6%)
Least common
- heart attack (0%)
- advanced cancer (1.1%)
- childbirth (1.1%)
Pain (in some form) is experienced by ___ of the population
100%
Around ___% of the population have had chronic pain in their lifetime
50%
Around __% have chronic pain right now
20%
Explain prevalence vs incidence
prevalence = current cases
incidence = new cases
explain out-patients vs in-patients
- Out-patients: given a prescription that you take home
- In-patients: people being treated in the hospital
Explain the back pain and NHS pyramid
surgery: 24,000
in-patients: 100,000
out-patients: 1.6 mil
consulting GP: 3 mil-7 mil
population prevalence: 16.5 mil
Explain prevalence of pain - headache in children study
- Type of population: schools, general practice, community, girl schools
- Studies had very different sample sizes (1,000-10,000)
- Age ranges are different
- Migraines range from 3%-10.6%
Explain self-reported prevalence of specific CHRONIC CONDITIONS by sex, household, and population aged 15 years and older, Canada 2007-2008 (most and least common)
Most common:
- back pain
- high blood pressure
- arthritis
Least common:
- alzheimer’s/dementia
- stroke
- cancer
Prevalence of pain by body part
Head = 15%
Neck = 8%
Upper back = 5%
Hip = 8%
Lower back = 18%
Shoulder = 9%
Leg = 14%
Hand = 6%
Knee = 16%
Describe the burden of pain
- functional activities (sleep, work, household, leisure, energy)
- social consequences (martial, family, intimacy, social isolation)
- Socioeconomic (healthcare costs, disability, productivity)
- emotional (irritable, angry, anxious, depressed)
Explain types of pain vs difficulty with basic/complex actions (%)
- severe headache or migraine: 31/33.5
- lower back: 51.6/55
- neck pain: 30.2/34.4
- knee pain: 37.7/38.6
- shoulder pain: 17.7/21.4
- finger pain: 14.3/16.3
- hip pain: 15/18.4
What are the most and least common social dislocations among chronic pain patients?
Most common:
- postponed housecleaning (81%)
- postponed household duties/laundry (79%)
Least common
- stayed in bed (18%)
- decline in sexual relations (24%)
What is comorbidity?
the likelihood that one disease is linked with another
Which kind of patients experience significant comorbid symptoms?
Patients with peripheral neuropathic pain
Why does chronic pain costs more than heart disease, cancer, and diabetes?
- Because of scans, x-rays, CTs, etc.
- Biggest economic burden: employment costs (amount lost to the economy because they couldn’t go to work and someone had to leave work to take care of them)
Explain pain in Abrahamic religions
- Pain as punishment for sin (Eve ate the apple)
- Pain as redemption (Jesus)
- Pain as personal atonement/redemption (Muslim)
Aristotle view of pain
pain is an emotion, in the heart
Galen view of pain
pain is a sensation, in the brain
Avicenna view of pain
pain is an independent sensation from touch/temperature
Descartes view of pain
there exists a “pain pathway” from the body to the brain
What is the order of philosophers regarding pain?
Aristotle
Galen
Avicenna
Descartes
What is theodicy?
an attempt to justify or defend God in the face of evil
What is dualism?
Mind and body are separate
What is monism?
Mind and body are together
People should have the right to:
- Access to pain management without discrimination
- An acknowledgement of their pain and to be informed about how it might be assessed
- To have access to appropriate assessment and treatment by trained healthcare professionals
Pain in art - what was the name of the work?
“The Broken Column” by Frida Kahlo
Name the top 3 and bottom 3 countries for opioid consumption
Top:
- Canada
- Switzerland
- Germany
Bottom:
- Egypt
- Venezuela
- West Africa
Until _____ there was no generally accepted definition of pain
1979
What does the IASP stand for?
IASP: international association for the study of pain
What is masochism?
non-unpleasant pain
What is a drive state?
Something that compels action
What are adequate stimuli for the other 4 senses?
- For vision: photon
- Audition: air pressure changes on eardrum
- Olfaction: any odor in environment that you have an olfactory receptors
- Taste: 5 tastes, rest are combos of them
What is the adequate stimulus for pain?
- Mechanical pressure
- Inflammation
- Noxious cold/heat
- Any number of natural compounds/chemicals in the environment
- Skin damage
Why does surgery hurt after patient wakes up?
- Inflammation
- Actual tissue damage
What causes pain for the colon?
Distention, NOT heat
Why can brain surgery can be done through local anesthetic ?
after the meninges, there’s no pain felt
What is neuropathic pain?
pain due to damage of the nervous system itself, usually the peripheral NS
The old definition of pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
The new definition of pain
An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.
Difference between anesthesia and analgesia
- Anesthesia (local): no pain, no touch, no heat, nothing. (no sensory transmission at all)
- Analgesia: no pain
(All analgesics are not anesthetics)
What is nociception?
Not pain – the workings of the nervous system that eventually lead to the perception of pain
- The neurons and their firing
- The biological happenings that eventually lead to pain
What things maybe have pain?
Worms, primary cortex, or any part of the cortex
Explain the thermal grill illusion
- If you touch an individual tube you won’t feel anything
- If you took multiple, you feel pain
- There’s no noxious stimulus
- Example of how pain can be constructed
Describe Fordyce’s Behavioural Model of Pain
nociception –> pain –> suffering –> pain behaviour
Why do we have acute pain? (seconds to minutes)
- It enables us to avoid or minimize tissue damage
- It’s a teaching signal (one-try learning)
Why do we have tonic pain? (hours to weeks)
- To motivate you to rest and recover
- Wounds heal better if you don’t move (especially broken bones)
Why do we have chronic pain? (weeks to years)
- There’s no reason, it’s a pathology (which means that something’s gone wrong and that it has no function at all)
- It’s like a broken smoke alarm that’s stuck on even though there’s no smoke
What is anhidrosis?
inability to sweat
- usually associated with congenital insensitivity to pain
Average lifespan of people with Congenital sensitivity to pain
38 years
How do most people with congenital insensitivity to pain die?
Most die from repeated hip fractures, which leads to infection (sepsis)
Explain the lumping and splitting problem
One thing to study (lump) vs multiple things to study (split)
Pain becomes chronic when it has lasted for ___
3+ months
What is etiology?
the underlying reason for something
What is nociceptive pain?
- pain where there is no NS lesion but also no inflammation
- evoked by high intensity stimuli
What is inflammatory pain?
Inflammatory: pain with inflammation
- more noxious stimulus –> more pain (stimulus dependent)
What is dysfunctional pain?
no known NS lesion and no inflammation
- sensory amplification
- present with lack of stimulus
- AKA noci-plastic pain
What is neuropathic pain?
NS lesion or disease of NS
- Pretty much the same as inflammatory
- Pain with no stimulus
What are the types of chronic pain (on the graph)?
Nociceptive (inflammatory), neuropathic, visceral, mixed
What is superficial pain?
Skin pain
What is deep pain?
In the muscles, joints, bones
What is visceral pain?
Pain in the viscera (internal organs)
- Often feels like it’s somewhere else, like the surface
Where do you feel neuropathic pain?
You feel it in the skin territory that the nerve serves (this can be a very different place)
What is phantom limb pain?
the pain is located in space (ex: where their hand should be but isn’t)
What is spontaneous pain?
- Pain coming from the inside by itself (you don’t need to do anything for it to hurt)
- Nothing needs to touch it to hurt
- Could be continuous or paroxysmal (happens sometimes but goes away)
- Most common type of pain but we know the least about it
What is evoked pain?
pain hypersensitivity to various types of touching
What is allodynia?
People with allodynia are extremely sensitive to touch
- Things that don’t usually cause pain can be very painful
What is hyperalgesia?
An increased sensitivity to feeling pain and an extreme response to pain
Difference between static and dynamic stimulus
Static: unmoving stimulus / Dynamic: moving stimulus
- dynamic more common (activity evoked)
What is numbness?
anesthetic in a body part (no feeling)
What is paresthesia?
a funny feeling that’s not pain but not normal (non-unpleasant tingling)
What is dysesthesia?
Paresthesia that you find unpleasant
Ex: your arm falls asleep
- Both are symptoms of chronic pain disorders
What is a paradoxical thermal sensation?
when a cold/hot sensation feels hot/cold
What is an aftersensation?
a sensation that lasts longer than it should
What is mechanical allodynia?
When a normally non-noxious stimulus is now noxious
- someone touching your back when you have a sunburn
What is mechanical hyperalgesia?
Noxious to more noxious
Ex: having a shower that’s too hot (noxious) –> with a sunburn (more noxious)
Explain the difference of hyperalgesia vs allodynia
Allodynia = pain due to a stimulus that does not normally elicit pain
Hyperalgesia = increased pain from a stimulus that normally provokes pain
Explain the difference between a sign and a symptom
Sign: something that the clinician observes themselves
- Requires examination
Symptom: something that a patient complains of
- Requires interview
Explain most and least common in Relative Frequency of Signs & Symptoms
Most:
- deep pain
- ongoing pain
- evoked pain
Least
- Touch-evoked pain
- Moving stimuli pain
- Warmth-evoked pain
Summarize Crook et al study
- Put squid in a tank and let in a bass (who eat squid)
- In 30 min, the bass picked off 4 out of 20 squid
- Mere presence of anesthetic = no effect
- Injured squid: 11 out of 40 eaten
- Injured + anesthetic = even more got eaten
- Inhibiting pain made it worse
- Chronic pain causes hypervigilance to remind
you you’re injured so you’re more careful - Injured were more careful
What is trephination?
- Idea is that pain was caused by evil spirits in the brain
- The only way to let them out was to drill a hole in people’s skulls
What is theriac?
reduces pain because of the active ingredient opium
In 1500 AD, pain was treated with ____
Pain was treated with willow bark (generally boiled into a tea) or opium poppy (which could be drunk straight from a plant)
What was the first pharmaceutical company called?
Merck
- founded in 1668 in Darmstadt, Germany
- Came up with a process to make standardized doses of morphine
Explain the significance of “Ether Dome” (1846)
Was a surgical operating ampitheatre in the Bulfinch Building at Massachusetts General Hospital
- Before this, people had surgeries without anesthetic
- The event occurred when William Morton, a local dentist, used ether to anesthetize Edward Abbott
- John Warren, the first dean of Harvard Medical School, then painlessly removed part of a tumor from Abbott’s neck
What is opioid?
Things that are like opium
What is equianalgesic?
that dose at which two opioids (at steady-state) provide approximately the same pain relief
What is half-life?
time it takes for ½ the drug to still be in your system
What is the half-life of methadone?
4-8 hours
What is subcutaneous?
into the skin
What is intravenous?
into but not through the vein
What is transdermal (topical)?
patch put on the skin (adv: less side effects)
What is implantation?
pump shooting right into the dermis
What is intrasynovial?
into joint
What is intracardiac?
into the heart
What is intrathecal?
into spinal cord
Why are there so many roots of drug administration?
It’s a matter of time and where it needs to go
What is the difference between pharmacokinetics and pharmacodynamics?
Pharmacokinetics: what the body does to the drug (ADME)
Pharmacodynamics: what the drug does to the body
What does ADME stand for?
Absorption
Distribution
Metabolism
Elimination
What is Patient-controlled analgesia (PCA)?
IV unit that releases drug into IV drip
- People use a lot less when they can control it
What are the most and least common side effects for opiates?
MOST:
- Constipation (biggest problem – 80%): can produce pain that may rival the pain you started with
- Nausea or vomiting
- Sedation
LEAST:
Dry mouth
Urine retention
Pruritis: itch
Why would OTC analgesics not be approved today?
they can cause serious liver damage
Why are OTC analgesics available?
they were introduced a long time ago when we weren’t as concerned with side effects
What does dextromethorphan treat?
Cough
- Doesn’t do it very well
- No evidence it really works at all, but doesn’t really cause any problems
What does metastatic mean?
Goes into your bloodstream
Explain the WHO analgesic ladder for cancer pain
Level 1: pain
- non-opioid, +/– adjuvant
Level 2: pain persisting or increasing
- weak opioid, +/– adjuvant, +/- non-opioid
Level 3: pain persisting or increasing
- strong opioid, +/– adjuvant, +/- non-opioid
—> freedom from cancer pain
What can steroids help treat?
inflammation
What can antidepressants help treat?
Effective for treatment of chronic pain
- The dose is different for pain vs depression
The treatment of chronic pain is often the drug that:
was developed for something else
Explain otomies and ectomies
when you cut something (doesn’t work very well for pain because you can’t cut everything and there are a lot of roots)
Explain the Anesthesiological method of blocks
Taking a local anesthetic and injecting it somewhere where it’s going to prevent the pain signal from being transmitted
- Extremely effective, at least at first
- Question of how long they’ll last
What is the western default medicine?
allopathic medecine
(opposite of complementary/alternative)
Why are data for complementary pain medicine hard to find?
they aren’t drugs, so they’re hard to prove
- Once it’s proven, its no longer complementary medicine (turns into allopathic medicine)
Summarize Stephens et al
if people were put in pain and told to swear vs not swearing, those that were allowed to swear reported lower pain
Summarize Guetin et al
if people were allowed to listen to music while being put in pain, they reported lower pain levels than those in the control group
Name some self-management behaviours for coping with pain
- exercise
- pacing
- relaxation
- assertiveness
Explain the story of Jeffrey Lawson (1985)
In 1985, that baby had open heart surgery without anesthesia, but it was given a muscle paralyzer
- This was because doctors didn’t believe that babies felt pain
- The baby died
What is the only way to get blood from babies?
heel lance
What does analgesic mean?
to relieve pain
What methods are analgesic in babies?
Sucrose, breastfeeding, and kangaroo care – holding the baby against bare skin
Who is John Bonica?
- Used to be a wrestler (he was 4’11)
- Wrote the first-ever textbook of pain called “The Management of Pain”
- Came up with the 1st multidisciplinary pain clinic
Explain difference between curative and palliative intent
- curative: treatment to cure
- palliative: treatment to lessen symptoms and pain (patient will probably end up dying)
What is a vital sign?
something that a nurse is required to write down every time the nurse visits the patient in the hospital
- pain was introduced as the 5th vital sign
Explain the pyramid of evidence-based medicine
TOP
systematic reviews and meta-analyses
randomized controlled double-blind studies
cohort studies
case control studies
case series
case reports
expert opinion
personal opinion
BOTTOM
Why are Case reports better than expert opinions ?
because someone has written it down (and published)
What is a case series?
More than one case report and you write a paper about what you’ve done
Why are Randomized control double-blind study (RTCs) not at the top of the pyramid?
not at top since sometimes they disagree with each other
What are meta-analyses?
a bunch of RCTs (has to be a bunch of good ones)
The gold standard of meta-analyses are done through the _______
Cochrane collaboration
Explain the steps of RCTs
- Enrolment (assessed for eligibility + randomized)
- Allocation (receive intervention)
- Follow-up
- Analysis
What are the inclusion criteria for RCTs?
you have to have pain levels above a certain number
What are the exclusion criteria for RCTs?
already received treatment, haven’t had pain for long enough, comorbidities, etc.
Explain the 3 arm experimental design
- 1 group placebo, 1 group active control, 1 group experimental treatment
- Parallel design: groups are being run in parallel
- Double-blind procedure
Explain the crossover experimental design
- Two groups and two phases
- All participants get both drugs
- Advantage: more powerful statistically (you can compare everyone to themselves), you can use less people because of this
- Disadvantage: it may matter what order the drugs are given in
Difference between crossover and parallel
parallel: cleaner / crossover: more powerful
Explain the enriched experimental design
- Enroll people into your study, and everyone gets the real drug
- You raise the dose until everyone responds (as long as there are no intolerable side effects)
- Only at that point are they randomized where half takes placebo and half take the drug
- May not be predictive of drug working in the real world
Summarize Lidoderm study
- 3 groups in study
- Placebo had just as much pain relief after two hours, but Lidoderm appears to beat placebo
What was the patient preference for Lidoderm vs placebo?
Lidoderm: 78%
Placebo: 9%
How long did patients use the lidoderm vs placebo patches?
Lidoderm: used 14 days
Placebo: used for 6 days
- Does longer or shorter use indicate how well it worked for pain?
Explain odds ratios (relative risk)
Big question: the proportion of who gets cancer and who doesn’t
no link to cancer (denominator) / link to cancer (numerator)
result: (?)x more likely to get cancer than people in population B
What is the odds ratio (rlative risk) equivalent for analgesic pain?
drug and placebo
What does relative risk of 1 mean?
nothing
Explain the forest plot of relative risk to wheezing
- Relative risk shown by squares
- Size of squares show how big the study was
- Two lines: 95% CI
- One study had no bars overlapping
- The others didn’t which means that these studies didn’t necessarily work
- Conclusion: this intervention does not affect parent-reported wheezing
What happens when every study is above diagonal in the l’abbe plot?
higher percentage were more responsive to drug than placebo
Can conclude that drug works
What drug seems to work on the l’abbe plot on the right?
Amitriptyline
What is a l’abbe plot?
A type of meta-analysis
What is number needed to treat (NNT)?
You need to treat (x) patients to get one to respond that wouldn’t respond to a placebo
- How much extra advantage does the drug give over a placebo
ex: NNT of 4 –> 1 in 4 patients
What is the NNT formula?
1/(proportion benefitting from experimental intervention - proportion benefitting from a control intervention)
OR
1/(patients responded to treatment/total patients receiving treatment) - (patients responded to control treatment/total patients receiving control)
What is paracetamol?
what they call acetaminophen in Europe
Explain Finnerup et al graph
- Pfizer funded really big trials to show that gabapentin/pregabalin worked (NNT ~5)
- Challenges the notion of what it means for the drug to work
What is the NNT of peptic ulcer?
1.1
curing ulcers a year later: 1.8
NNT of antidepressants
4
NNT of Painful diabetic neuropathy
2.9
NNT of low dose aspirin
40 (you need to treat 40 people to prevent 1 death)
- Why use it?
- It’s for trying to reduce the number of heart attacks in SOCIETY, not just you
- Through a societal perspective, NNT of 40 is fine
Where on a graph would the perfect analgesic lie?
Top left corner –> want NNH to be low but NNT to be high
How to calculate NNH
1/(proportion reacting from experimental intervention - proportion reacting from a control intervention)
What is an equivalent measure of NNT?
effect size
Explain first line, second line, ect. drugs
If patients don’t respond to first-line drugs, then move to the second, then so on
Why are there so many anesthesiologists in the IASP?
The neurologists and rheumatologists have their own associations
What two journals does IASP publish?
PAIN and pain reports
Why are there more neuropathic (6%) than arthritis (3%) studies?
neuropathic more attractive to neuroscientists
What is the dorsal root ganglion?
collection of cells that is just outside of the spinal cord
Why is dorsal important for pain?
Sensory info goes up dorsally and motor info comes down ventrally
What are ascending pathways (the “pain matrix”)?
- thalamus
- somatosensory cortex
- limbic cortex
- prefrontal cortex
What are pain-relevant loci (for pain below the neck)?
- skin/muscle/joint/viscera (“periphery”)
- dorsal root ganglion (DRG)
- dorsal horn of the spinal cord
- brain
What are descending pathways (not motor)?
- hypothalamus
- midbrain
- brainstem
- spinal cord
Why have descending pathways?
- The brain wants to have some control over its input
- It sends info back down to the spinal cord
What is glabrous skin?
skin only on palms of your hand and soles of your feet
What initiates pain sensations?
Specialized Schwann cells
(as well as free nerve endings)
What is a bipolar neuron?
cell body in middle, one side axon terminal and other side dendrite
What is a multipolar neuron?
Many dendrites and one axon
What is a unipolar neuron?
There’s one line that goes from dendrites to axons on other end, cell body on the side
Where do the longest primary afferent neurons go?
up your toe to your spinal cord
what are primary afferent neurons?
first neuron going up (sensory info)
Why do some pain syndromes show a “glove and stocking” distribution (starts at the feet and goes up)?
- The longest nociceptors in the body are the ones coming from the feet
- The longer the neuron = the more fragile
afferent vs efferent
afferent: from the periphery up to the CNS
Efferent: going down from higher levels of CNS out to the periphery (how the NS controls the muscles)
What do the A afferent fibers have?
Myelin (c does not)
a-alpha
Speed: 100m/s
For proprioception (feeling where your body is)
a-beta
for touch/vibration
a-delta
Speed: 25 m/s
For thermal and pain
c fibers
Speed: 1 m/s
For pain and sweating
what is first and second pain mediated by
- First pain: mediated by A-deltas (instant)
- Second pain: Cs (dull but lasts longer, because they’re slower)
- The route is much longer
what keeps axon bundles alive?
blood capillaries
rostral
towards the head
caudal
towards tail
dorsal
towards back
ventral
towards stomach
anterior
front
posterior
back
medial
towards midline
lateral
to the side
ipsilateral
on the same side of
contralateral
on the opposite side to
cervical
closest to brain
thoracic
upper back
lumbar
lower back
sacral
hips, genitals
what does t1 to t2 divide
divides chest from belly button
primary afferent fibers going in at t2 are:
carrying sensory info from that part of the skin
efferent fibers coming out of t2 are going to:
control muscles
what is shingles?
very restricted and painful rash
why does the vertebra have to be broken up?
because the spinal nerves need a place to get out
ventral root and dorsal root converge into:
a mixed spinal nerve
ventral root is where:
motor neurons are going out to the muscles
dorsal root is where?
sensory info is coming in from the periphery to the spinal cord up
what kind of nerve is the spinal nerve?
mixed nerve (afferent and efferent)
spinal ganglion is the same thing as:
dorsal root ganglion
what is a ganglion?
a collection of neuron cell bodies that’s outside of the CNS
The spinal ganglion is a bulge –why?
Cell bodies are bigger than axons, hence the bump
spinal cord is covered with:
meninges
what is the hole in the middle of dorsal root ganglion?
cerebral spinal fluid
what is the central canal
where cerebral spinal fluid goes
function of dorsolateral fasciculus
where primary afferent are coming in
what is the substantia gelatinosa?
laminae 1 and 2 looped together
Explain the journey of sensory info
dendrites in skin –> primary afferent neuron –> DRG –> SC + dorsolateral fasciculus –> 2nd order neuron –> CNS
function of 2nd order neurons
fire, cross, ascend
- either in laminae 1 and 2 OR 5 and 6
what is between primary and 2nd order neuron?
interneuron
what are the 2 classes on c fibers?
CGRP+
IB4+
what is NeuN?
makes all neurons fluorescent
what lights up in CGRP?
dorsolateral fasciculus in laminae 1
what lights up in IB4?
dorsolateral fasciculus in laminae 2 (more restrictive stain)
what does Nav1.7 light up?
all nociceptors
where do a-betas terminate?
mostly in lamina 3 and 4 and maybe a bit in 5
where do a-deltas terminate?
some going to 1 and some going to 5
where do Pepditergic c fibers terminate?
in 1
where do non-Pepditergic c fibers terminate?
in 2
what was the modern molecular definition of sensory neurons defined by?
defined by single-cell RNA-sequencing (i.e., gene expression) of DRG cells (followed by principal components analysis (i.e., clustering)
- 622 neurons
How many neurons does the category of TH have?
233
what does NF mean
neurofilamentary heavy chain
what does NP mean
non-peptidergic
what does PEP mean
peptidergic (2 categories)
what does TH mean
tyrosine hydrolase-expressing (1 category)
what is the efferent function of nociceptors?
Produces neurogenic inflammation
- When a nociceptor being stimulated by noxious stimuli, AP is going up and going towards CNS
- They also have collateral branches, where things can be released at the end (efferent function)
- Released: CGRP and substance p (SP)
- Both are good at making arterioles dilate, leading to plasma extravasation (fluids that were inside the arteriole now get released out into the tissue)
what is the purpose of plasma extravasation?
to release white blood cells to cause an immune response to deal with the wound causing the noxious stimulation
reflexes bypass the brain by:
spinal reflex
how does spinal reflex work?
Sensory neuron goes into dorsal horn –> interneuron –> motor neurons –> muscles –> withdrawal of limb
why don’t we study spinal reflexes?
We don’t study them because we don’t want to modify them (we want to preserve them)
The higher you go, the more:
white matter
in terms of columns, sensory info goes up:
in dorsal column or anterolateral column (where fibers of 2nd order neurons are)
what is a tract?
in the CNS whenever fibers go from one place to another long distance
spinothalamic tract
SC to thalamus
- Sensory info (in general)
spinoreticular tract
SC to reticular formation (midbrain, pons, medulla) – most deadly area to have trauma
- function: God knows
spinoparabrachial tract
SC to a particular nucleus in the pons called parabrachial nucleus
- Emotional pain info (general)
what is somatotopy?
the principle by which the location of the neural info corresponds to the part of the body it came from or is going to
explain the trigeminal system
- Parallel system, just above the neck
- In cranial nerve 5 (hence the V)
V1, v2, v3 - Trigeminal ganglion
- A-detas and cs project to the brainstem
- Lower part of brainstem is equivalent to spinal cord
what is the NTS (nucleus tractus solitarius) important for?
important for visceral sensation
what is the most complicated pathway? why?
visceral
- because sometimes they go to their own ganglia (that’s nowhere near the SC) to ganglia near the SC
explain somatic vs visceral fiber termination
Somatic: they terminate very specifically
- Easy to identify where pain is
Visceral: fibers terminate in a more diffuse pattern
- Why its hard to precisely localize visceral pain
- Has the ability to affect a lot of second-order neurons
visceral pain is:
referral
what is ischemia?
lack of blood supply
what is distention?
pain when plugged up or blocked
Somatic and visceral info terminate on:
the same 2nd order neurons
where can muscle pain also be referred to?
to the skin
describe the first referral on a conscious patient
- Doctor was able to touch the part of the body 12 inches away from where it was hurting
- If you inject saline that’s too hypo/hypertonic it’s painful
what is pain far away from injection?
referred pain
what is the first and oldest brain mapping technique
lesions
- induced: lesion on purpose
- TMS: reversible lesion of the brain
what is stimulation?
measuring electrical signals
- EEG, MEG (indirect)
- electrodes, optical imaging (direct)
what is the most popular brain mapping technique
hemodynamic (blood and oxygen)
- PET, SPECT, FMRI (so popular because you can do things over a big range of space and time)
which brain mapping techniques cause no damage?
fMRI and ERP
how was the pain matrix discovered?
using fMRI
- Problem: these parts aren’t just for pain
- Nonetheless, these parts light up when people are in pain
what does the difference in brain activation between normal subjects and clinical pain subjects suggest?
Suggests pain matrix is just for experimental pain and the PFC is more suggestive of clinical pain
name the percentages of pain in normal pain subjects
ACC 87%
Som 1: 75%
Som 2: 75%
Insula: 94%
Thalamus:80%
Pre-frontal: 55%
name the percentages of pain in clinical subjects
ACC: 45%
S1: 28%
S2: 20%
IC:58%
Th: 59%
PFC: 81%
explain the results of the motivational-affective aspects of pain study
- After suggestion for intensity: som 1 went up and down
- After hypnotic suggestion for unpleasantness: anterior cingulate cortex went up and down
why does pain pathway split in two?
because they can be independently manipulated
what are the S-D aspects and the M-A aspects of the hypnosis study?
S-D:
- localization of pain
- quality of pain
- intensity of pain
M-A:
- unpleasantness
- meaning of pain
explain the modern view parts of the pain matrix
Sensory discriminative
Motivational
Affective
Cognitive
Descending modulation
Inferential
what are the two descending systems (pain modulatory pathways)?
1: PAG, RVM, dorsal horn of spinal cord
2: midbrain, pons (locus cerulea), dorsal horn of spinal cord
what is the specificity theory?
there exists primary afferent neurons that don’t respond to anything but noxious stimuli
- The more noxious, the more they fire until it fires the fastest it can fire
what is the intensity theory?
the same neurons will fire weakly, but when the stimulus is noxious, they’ll fire much more
- The amount of firing is coding the strength of the stimulus
- There are nocicpetors that are specific more different modalities to pain (heat, cold, mechanical)
what is the pattern theory?
there are just primary afferents, its at higher levels of the NS that different firing of the neurons is decoded
- Its only then we’ll figure out what kind of stimulus it is
- The patterns tell us if it’s pain and what type
- Info is not in any particular afferent neuron
what paper did wall and melzack publish?
“Pain mechanisms in new theory”
explain the gate control theory
More activity in small –> gate open (pain info)
More activity in large –> gate closes (no pain info)
SG: interneuron in gelatinosa
- Large: excites it –> T inhibition –> no pain
- Small: inhibits it –> T excitement –> pain
what are large/small fibers in gate control theory?
Large fibers: a betas – touch info
Small: Cs and a deltas
what is an SG neuron in gate control theory
neuron in substantia gelatinosa in spinal cord
gate control theory: what happens when both small and large fire?
- It matters which wins the battle of large vs small, but if there’s enough large input you’re going to inhibit the T neuron
How does this explain why people rub where it hurts?
Rubbing (touching) increases L input, thus inhibiting s input, which inhibits T (pain sensation)
what is electrophysiology?
looking at neurons and how they fire
what is Microneurography?
Electrophysiological Recording of Primary Afferent Fibers (in humans)
- You can record form c fibers in humans right from the periphery
- Why can’t you record any higher in humans?
- It’s unethical, no one wants to do it obviously
Explain the graphs in the electrophysiological recording of dorsal horn cells
Left: dorsal horn firing more and longer the hotter the stimulus is
Right: sin-1 firing
- Brush stimuli: doesn’t fire much
- Press: fires little more
- Pinching: little more than that
- Fired to heat
what are the 3 different types of dorsal horn projection neurons?
Wide dynamic range: being excited by a-betas, a-deltas, and cs
- Basically the equivalent of intensity theory concept
- They will respond to a wide range of input
Nociceptive specific: only input from a-deltas and cs
Low threshold mechanosensitive: a-betas only
- touch is low threshold
- After injury (inflammation or nerve damage), it causes a change in the cells such that it turns them into nociceptors
- Instead of providing touch info to the brain, you feel pain
- Why they’re called silent nociceptors, because they have the ability to change into them
- Possible explanation for sensitization/allodynia
explain the Electrophysiological Recording of Anterior Cingulate Cells (with the rat)
- Squeezed the rat in 8 locations
- Wherever it was squeezed, that neuron fired
OR that cell has a receptive field of the entire body, because it doesn’t really matter where you put the noxious stimulus - The cingulate doesn’t care where the pain is, it only cares that there’s pain
What is CPM?
conditioned pain modulation
- pain inhibits pain (counter-irritation)
what is Transcutaneous Electrical Nerve Stimulation (TENS)?
a unit with pads placed on skin
- Doesn’t work super well, but works at least a little (maybe placebo)
- Electricity penetrates the skin
- A-beta fibers have their nerve endings a lot closer to epidermis than a-deltas and cs
How does gate control theory explain TENS?
TENS current increase L input, but don’t affect S input (bc the current can’t penetrate far enough)
- Works the same way that rubbing works
what is the sciatic nerve?
Mixed nerve
Serves the foot and back part of the leg
what is sensitization
the longer pain goes on, the worse it gets
what is skin-nerve preparation?
Recording and stimulating skin directly with a noxious stimulus
who was the first person to do central sensitization?
clifford woolf
difference between peripheral and central sensitization
Primary afferent: peripheral sensitization
- If primary fires more, dorsal horn in CNS will fire more (only because its getting more input)
2nd order: central sensitization (injury only in CNS)
- dorsal horn neuron will fire more but no change in primary afferent (not sensitized in periphery)
explain the Woolf sensitization study
Ipsilateral: after injury dorsal horn neurons fire more and for longer
Contralateral: DORSAL HORN Neurons also fire after injury, but basically not at all before (caused an increased sensitivity to the right leg)
- Due to changes within central nervous system
what is wind-up?
the more stimuli you give, the more the neurons fire (sensitization basically)
what is temporal summation?
noxious stimuli summating in time as long as stimuli are close enough together
what is spatial summation?
More probes that are simultaneously going off, more pain reported
primary vs secondary hyperalgesia
primary: site of injury (peripheral sensitization)
secondary: site around injury (central sensitization)
what is the flare?
redness around injury
two types of secondary hyperalgesia
- Inside zone: stroking hyperalgesia (but not punctate) – if you take a paint brush in the area and people say that hurts
- Outside zone: punctate (take a q-tip and poke straight down)
- Area of punctate is wider than stroking (you can get it in stroking too)
You can show mechanical secondary hyperalgesia but not heat secondary hyperalgesia - Why?
LTM neurons (low mechanical threshold)
what is mirror pain
central sensitization
structural vs functional plasticity after injury
functional: possible changes of function
structural: possible changes to dendrites or terminals
explain the difference in positive/negative scores in regards to CPM
Negative score: CPM working (normal)
- Didn’t respond to drug
- You already have as much internal pain inhibition
- CPM is reflective of your natural pain inhibition systems
Positive score: CPM not working
- Instead of becoming analgesic, they became hyperanalgesic (CPM wasn’t working)
- Duloxetine (drug) worked
explain chronic pain and CPM
- People with chronic pain syndrome show less CPM than normal
- Fibromyalgics had impaired CPM
