Midterm 1 Flashcards
Pain in numbers
1 reason to seek health care
#1 concern of patients with chronic disease
Most present in knee, head, lower back
Most limiting in terms of basic and complex actions
Prevalence
Incidence is how many new patients
Prevalence is the number who have it considering deaths + recovery + incidence
Number of prevalence depends on who you ask (national survey, vs doctor, vs patients). Need meta analyses of all of these to average them
Chronic pain on lifespan
Everyone is dying of the same thing but having chronic pain makes cardiac arrest or cancer more likely and therefore more people are dying (especially for widespread pain)
Pain in philosophers
- Aristotle: pain is an emotion in the heart
- Galen: pain is sensation in the brain
- Avicenna: pain is independent sensation from touch/temperature
- Descartes: pain pathways from body to brain
Pain and Utilitarianism
Cost-benefit
Consequences
Part of the math of your decisions (based on amount of pain and pleasure it will bring)
Peter Singer
Animal rights
The fundamental interest that entitles a being to equal consideration is the capacity for suffering and/or enjoyment or happiness
Human Rights (Declaration of Montreal)
Article 1: The right of all people to have access to pain management without discrimination
Article 2: the right of people in pain to acknowledgment of their pain and to be informed about how it can be assessed and managed
Article 3: the right of all people with pain to have access to appropriate assessment and treatment of the pain by adequately trained health care professionals
Old Definition of Pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
*
#1: not always unpleasant
#2: not a sensation like the other ones ( it never habituates it just gets worse (sensitization), and stimulus and response rarely match). Also carries emotions differently than the others
#3: can hurt when trying to limit tissue damage
#4: some people might not be able to describe their pain
New definition of pain
An unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage
So doctors can infer
What’s NOT pain
- Somatosensation (just touch)
- Anesthesia (absence of all feeling) vs Analgesia (absence of pain)
- Emotional and physical pain overlap but not same thing
- Pain causes suffering and disability but not the same thing
- Pain behaviour is not necessarily related
- Nociception produces the perception of pain
The thermal Grill illusion
Example of pain without Nociception
Put your whole hand is painful (freezing sensation) but each tube on its own is not painful
Fordyce’s Behavioural Model of pain
Nociception -> Pain -> Suffering -> Pain behaviour
The further you go up depends more on other factors, down depends more on biological
Why pain (3)
From evolutionary point of view:
- Acute pain (sec-min): prevent tissue damage, prevent infection (leading cause of death), teaching signal of what you can’t do again
- Tonic pain (hours-weeks): rest and recovery (by punishing the movement)
- Chronic pain (weeks-years): no adaptive significance (a disease)
Possible answer: pain increases survival of squid with missing leg (more vigilance, take less risks)
Lumping vs Splitting
Can either lump as the same things to make learning more easy (but might miss out on important info because they might be different in some ways), or split to have more precise info but longer and could be unnecessary
Ways of Splitting the Pain: Duration
- acute up to 30 days
- chronic over 6months
- subacute for in between
Ways of Splitting the Pain: Etiology
Causes:
- nociceptive (stimulus dependent, no lesion or inflammation)
- neuropathic (nervous system lesion, lasts longer)
- dysfunctional (no lesion or inflammation, spontaneous pain, present without stimulus)
- inflammatory (active inflammation, already hurts))
Ways of Splitting the Pain: Location
- superficial (pressure)
- deep pain (muscle, bone)
- visceral (internal organs)
- neuropathic (feel skin but really nerve)
- phantom (feel in empty space)
Ways of Splitting the Pain: Symptoms
- Spontaneous pain: comes from inside (not affected by outside factor), continuous vs paroxysmal
- Evoked pain (pain hypersensitivity): Allodynia (heat, cold, mechanical, vibration) that is not noxious ie little slap on sunburn now hurts / Hyperalgesia (same but noxious) big slap on sunburn. Static/Dynamic.
- Paresthesia (weird feeling) / Dysesthesia (weird unpleasant feeling)
- Numbness
- Paradoxical thermal sensations (ice burns)
- After-sensations (hurts long after it should have stopped)
Sign vs Sympton
Sign is inferred from a test
Symptom patient tells you about it
Old treatments of pain
- Trephination (hole in skull to let evil spirit out)
- Theriac (weird mixture but contained opium poppy)
- 1500AD used Opium poppy (opioids) and Willow bark (aspirin) plants
- Anesthesia : Ether Dome first surgery patient asleep
Drug Administration
s.c. : subcutaneous (through skin)
i.m. : intramuscular (deep)
i.v. : Intravenous (hardest cause precise)
Transdermal (patch)
Implantation (tube)
Major difference is the timing
Side effects Opiates
Most common and problematic is constipation (80% prevalence)
Respiratory depression kills but rare
Worse of all is addiction
Over-The-Counter (OTC) Analgesics
- Acetaminophen (tylenol): not anti-inflammatory, just pain
- Aspirin + Ibuprofen (Advil) + Naproxen: anti-inflammatory
WHO ladder for cancer pain
1: pain -> non-opioid adjuvant
2: pain increasing -> opioid for mild to moderate pain
3: pain increasing -> opioid for moderate to severe pain
Can cure all pain cause max is anesthesia but then just sleep
Analgesic Categories
1- OTC (x24)
2- Opioid (x19)
3- Anesthetics (sodium channel -cain) (x10)
4- serotonin receptor (migraine) (x9)
6- voltage gated calcium channel (x3)
7- GABA (x3)
… (x1)
Treatment Choices
- Surgical: interventionalist, (-otomy cut in half, -ectomy take something out), moslty placebo
- Anesthesiological: nerve blocks (works but wears off quick)
- Physiological: CBT (frame things differently), most common
CAM Complementary Alternative Medicine
Mostly placebo, could work but heard to prove
Mindful, spiritual, energy based, stimulation based, movement based, manipulative, nutriceutical)
Multidisciplinary Pain Clinics
John Bonica
Works better all together
all at the same place
Palliative and Hospice Care
Go from curative intent to palliative intent when closer to death (goal is just to reduce the pain)
Evidence Based medicine
Personal opinion -> expert opinion -> case reports (info on 1 patient) -> Case series (series of reports) -> Case control studies (experiments) -> cohort studies -> RCT -> multiple RCT (meta-analyses)
Good place to find info is Cochrane Collaboration (meta-analyses)
RCT designs
Parallel design: eligible are randomly assigned to Drug vs placebo or drug A vs drug B, follow up, analyzed (includes lots of drop outs at each step, which could mean side effects, or that it works so well. Can throw out data or pretend like it followed its trend)
Crossover: both participants get both treatments (allows within-subject analysis which is better stats, but assumes no long-term effects that the drug washes out)
Enriched design: cheating because pre-selecting who it will work for
Odds ratio
Odds that ti worked vs it didn’t work
Estimate size of the effect
cancer exposed x no cancer unexposed (support relationship) DIVIDED BY cancer unexposed x no cancer exposed (no relationship) = 4 so 4 times more likely to get cancer if exposed
for pain:
50% reduction drug x less then 50% placebo DIVIDED BY 50% reduction placebo x less than 50% drug
Meta-Analyses: Forest Plots
Each line equals -0-, the bigger the box the bigger the study, weighted average losange at the bottom, left og 0 means it worked vs not,
Meta-Analyses: L’Abbe plots
Diagonale is drug does not work (under it if placebo worked better so drug is actually bad)
Each dot is a study (the bigger dot the bigger study)
Best effect top left
NNT Number needed to treat
1 DIVIDED BY (proportion benefitting from intervention) - (proportion benefiting from placebo) = 4 so have to treat 4 patients for 1 to respond (that hasn’t already responded to placebo) (which means more than 1 will get pain relief)
NNH Number needed to harm
Side effects
Perfect drug is at top left
GRADE
Recommendations guideline
Don’t even use numbers in the end, subjective recommendation (weak/strong, moderate/high)
IASP International association for study of pain
Mostly anesthesiologists (founders), publish PAIN journal
Mostly publish intervention purpose, and on human patients
Basic pain anatomy
- Important spots: periphery (skin, muscle, joint), DRG dorsal root ganglion, dorsal horn of spinal cord, brain
- Ascending pathways: periphery -> brain, thalamus, somatosensory cortex, limbic cortex, prefrontal cortex. The pain matrix
- Descending pathways: high brain -> low brain, hypothalamus, midbrain, brainstem, spinal cord. Not motor
Ascending and descending meet at spinal cord
Skin anatomy
Glabrous skin (palms) vs Hairy skin
There is different never endings that give them different modalities
Pain is through free nerve ending (nociceptor)
Nociceptors as unipolar neurons
- Multipolar neurons (98%): many dendrites and 1 axon, just pass on information
- Bipolar neurons: eye and ear, cell body in middle
- Unipolar neurons: 1 long axon with dendrites on both ends, cell body out int the middle, very ling and very fragile, leads to spinal cord/brain
Afferent fibers
Afferent: sensory, collect information (go up)
- A-alpha: thick myelin, very fast. Muscle control
- A-beta: thinner and slower. Touch and vibration
- A-delta: thinner and slower. Thermal and pain
- C: no myelin, slowest. Pain and sweating (also have small efferent function)
(Efferent fibers are motor, they go down)
Termination in Dorsal horn:
A-beta goes deep (4-5)
C goes to inner 2 or 1 if peptidergic (CGRP / IB4)
A-delta goes into 1 and 5
1st / 2nd pain
First pain is immidiate and sharp, caused by A-delta fibers
Second pain is more dull and lasts longer, by C fibers
Spinal cord anatomy
Top -> Bottom:
Cervical
Thoracic
Lumbar
Sacral
Medial (center) vs lateral (sides)
Ipsilateral (same side as) vs contralateral (opposite side as injury)
Fluid in the middle
Ventral is between 2 big, dorsal between 2 small horns
Dorsal root ganglion DRG
Made up of 2 horns: Posterior/Dorsal (thinner) and Anterior/Ventral (thicker)
3 layers of protection (dura mater, arachnoid, pia matter)
Root filaments come out (dorsal and ventral) that form mixed spinal nerve
DRG comes out of this (big ball)
Rexed’s Laminae
Division of horn into 9 sections
6 in posterior (small)
Last 3 in anterior (big)
Pain pathway
Pain fibers in skin -> primary afferent neuron -> DRG in spine -> terminates in I and II -> (interneuron that leads to another section) -> second-order neuron cross sides -> brain stem and thalamus
Other:
Spinothalamic: spine to thalamus
Spinoreticular
Spinoparabrachial: spine to pons
Modern molecular definition of sensory neurons
Classify them by gene expression using RNA sequencing
Found 11 types total to split a
Spinal reflexes
From skin to DRG to horn to motor neuron to muscle directly, take hand away faster for sharp stimuli
Somatotopy
Mapping of body into the brain
Trigeminal Anatomy
Over the neck
Works the same as under the neck but trigeminal ganglion instead of DRG
Visceral Anatomy
Organs
Multiple routes and very complex
Types of Afferent Fiber Terminations
- Somatic: from skin, very focused
- Visceral: from organ, very spread out all over the place (explains why it is so hard to describe organ pain)
Somatic-Visceral Convergence
Somatic Stimuli: mechanical, thermal, inflammatory
Visceral Stimuli: ischaemia (restricted blood flow), distension, inflammatory
Somatic Localisation: precise
Visceral Localisation: poor, referred to somatic structured (feels like it’s hurting somewhere it’s not, ie arm pain during heart attack)
The brain misinterprets because afferent visceral and afferent somatic seem to use the same second order neurons
Referred Pain
Feeling pain somewhere it is not
Skin pain is localised (but could be another point of skin)
Muscle pain can be localized or referred to skin or other muscle
Visceral Pain is always referred to skin/muscle/other part of viscera
Brain Mapping Techniques
3 ways:
- Lesions (natural or induced)
- Stimulation and Recordings (direct or indirect, ie electrodes or EEG)
- Hemodynamic Response (ie. PET, FMRI) measure flood flow, the more neurons firing the more blood flow
FMRI seems to cover the most ground
The Pain Matrix
Cortical Areas involved in pain
ie. M1 motor 1, S1 somatensory 1,…
But experiment have shown that none of these are ever 100% found activated during pain. Could just work for induced experiemental acute pain
Sensory-Discriminative vs Motivational-Affective aspects of pain
S-D: localization of pain, quality and intensity of pain
M-A: unpleasantness, drive to escape
Hypnosis study:
Anterior Cingulate cortex activity goes down when playing with unpleasantness M-A
S1 activity goes down when playing with intensity S-D
The Battle of the Theories
- Specificity theory: spinal cord neuron start firing at arrival of noxious stimuli and then gets worse as stimuli gets worse
- Intensity theory: the neurons fire MORE when noxious stimuli
- Pattern theory: (opposite of intensity), they are activated by everything in different combinations that then gets sorted out in the brain
- Gate-Control theory: type of pattern theory
They were all kind of right
Gate Control theory
check graph
Explains why rubbing feels good
Second-Order projection (Spinothalamic Tract STT) neurons
Important neurons that bring information to brain
- WDR wide dynamic range: go to Abeta + Adelta + C
- NS Nociceptive specific: go to Adelat + C (just pain)
- LTM low-threshold mechanosensitive: just go to touch Abeta. “Silent nociceptors” because turn into them after injury
CPM (Conditioned Pain Modulation (or counterirritation))
Use to find out how well ascending and descending pathways of pain work
Found that patients with less effective CPM reported higher drug efficacy (could be bc ppl with good working CPM are already dealing with the pain naturally)
Injured VS Uninjured Fibers
If you cut L5 for example, those nerves are gonna die and therefore make their terminal numb. But patients still feel pain because the dying nerves affected the ones next to it for L4/L6
Peripheral Sensisitization
Sensitization is the opposite of habituation (pain gets worse)
Inflammatory soup in the periphery sensitizes the nerves
Skin-nerve preparation (dead paw in water recordings)
Central Sensitization
Discovered by Woolf
Found that sometimes the changes happen in the spinal cord not on the skin by finding pain in the opposite leg of the injury
Temporal Summation
Bigger response to the same stimulus if it is repeated close to each other in time
You see more action potential at each stimulus
(Also works for Spatial summation if stimulus are close enough to each other, the more you add the more pain)
Primary vs Secondary Hyperalgesia and Allodynia
Primary: in the periphery, the exact spot of the injury, both mechanical and thermal stimulus need less to hurt than if no injury
Secondary: in the spinal cord, the hypersensitivity extends around the injury, only mechanical stimuli hurts more
So they’re different things
Two types of Secondary Hyperalgesia
Stroking: dynamic, light brushing or stroking hurts
Punctuate: static, only poking hurts
Means they have different mechanisms, but both are caused by central sensitization
Found that local anasthesia to the secondary area does not stop the pain which proves that it is happening in the spinal cord
Plasticity after injury (Functional vs Structural)
- Functional: molecular, synaptic, cellular, network (ie. firing patterns)
- Structural: something needs to be built/destroyed. Synaptic spines (more opportunity for connection), connectivity, cell number
Ectopic Firing
When they fire all on their own, best explanation for spontaneous pain