Lecture 3: Pain anatomy and physiology Flashcards
(104 cards)
1
Q
What was Descartes view of pain?
A
- Thread between the foot and the brain that allows you to pull your foot away when you feel it burning.
- Not exactly the case, but he is right that there is a pathway between the foot and the brain
2
Q
What are the pain-relevant loci? (for pain below neck because pain above neck isn’t the same pathway)
A
- skin/muscles/joints: places outside the NS where pain can start, “periphery”
- Dorsal horn of the spinal cord
- Dorsal root ganglion: part of the nervous system, outside of the spinal cord
- brain
3
Q
What are viscera?
A
- organs that can feel pain
- some can only feel certain pain
4
Q
Where does sensory and motor stuff happen?
A
- sensory stuff happens dorsal
- motor stuff happens ventral
5
Q
What are the two pathways of pain?
A
- ascending pathways, also called “pain matrix”: goes from the periphery to the brain
- descending pathways: not motor, modulated pain that goes from the brain to the periphery
6
Q
What parts of the brain are involved in each pathway?
Ascending: tslp
Descending: hmbs H n M Baby Section
A
- ascending: thalamus, somatosensory cortex, limbic cortex, prefrontal cortex.
- descending: hypothalamus, midbrain, brainstem, spinal cord.
7
Q
How is the skin roughly constituted (skin anatomy)?
A
- epidermis: top layer
- dermis: inner layer, has lots of skin in it
8
Q
What is the dermis composed of?
A
Different nerve endings:
- Meissner’s corpuscle, for touch.
- Pacinian corpuscle, for vibration
- Free nerve ending, very important for pain
- Schwann cells, also important for pain
9
Q
What important nerve endings is hairy skin composed of?
A
- Merkel’s disk, for touch.
- Ruffini terminals, for stretch.
10
Q
What is a nociceptor?
A
- Free nerve ending
- Specialised for response to pain
- unipolar neuron
- very long and very fragile cells
- distribute the pain in a glove-stocking style because long nociceptors will break first.
11
Q
How are unipolar neurons constructed?
A
- axon with cell body off to side, dendrites at one end of axon
- most of the body’s sensory neurons
- they collect information from energies in the environment.
12
Q
Why do some pain syndromes show a glove-and-stocking distribution?
A
Nociceptors in the foot or hand are the longest and are most likely to be damage. So the pain starts there and moves up gradually.
13
Q
What does afferent (fiber) mean?
A
- Sending sensory information up
- smaller ones
14
Q
What do efferent fibers do ?
A
- Send motor information down
- bigger ones
15
Q
What are the different types of afferent fibers ?
A
- proprioception: muscle control, Aalpha, 80-120 m/s
- touch, vibration: Abeta, 35-75m/s
- thermal, pain: Adelta, 5-35 m/s
- pain, sweating: C, 0.5-2 m/s, slower because of lack of myelination and small diameter
16
Q
What afferent fibers is responsible for first and second pain?
A
- Ad fibers, because transmission of info is very quick
- C fibers are responsible for second pain, which is why there is a delay cause information processing to the brain is very slow
17
Q
How are nociceptors organised ?
A
-Packed together in bundles called nerves (axons packaged together)
18
Q
What happens when you get pocked by a needle?
A
This will activate 1 maybe several nociceptors.
19
Q
What is shingles?
A
- Viral infection that causes painful rash
- Dermatomal specific pain
20
Q
What happens when you have pain on the left hand?
A
- Information crosses in the brain
- The pain will be integrated on the right side of the brain and vice versa
21
Q
How is the CNS protected?
A
- Shielded by bone
- There are holes in the vertebral column that allow spinal nerves to come in and out.
22
Q
What are the different spinal divisions?
A
- cervical: close to brain
- thoracic: upper back
- lumbar lower back
- sacral: pelvic area
23
Q
How does the spinal ganglion influence the physiology of the spinal cord?
A
-Makes dorsal root (afferent) thicker than ventral, because it needs room for cell bodies.
24
Q
What is the dorsal root ganglia?
A
- Mixed spinal nerve with efferents and afferents
- It is close to spinal nerve but not in spinal nerve
25
What is the "white matter" and why is it white?
- They are axons
| - It is white because the axons are myelinated.
26
What is the grey matter ?
- They are cell bodies
| - The ventral ones are larger than the dorsal ones because they are efferent muscle fibers
27
How is the grey matter divided?
- divided into 10 laminae according to shape, size and type of neuron that pass by each lamina
- 1 and 2: superficial pain
- 3 and 4: touch
- 5: deep lamina
28
What are the dorsolateral fasciculus?
- fibers that are entering the dorsal part from outside
- some come from primary afferents
- some come from the brain
- anything that enters the spinal cord enters here
29
What is the substantia gelatinosa?
- Not very dense
| - Corresponds to lamina 1 and 2
30
What are the two scenarios for information processing in the spinal cord?
Two scenarios:
- either it just goes through, or
- it can synapse (through an interneuron) in the subsantia gelatinosa to a second-order neurons (projection neuron).
31
What are the two types of C fibers?
- peptidergic: contains peptides, small protein neurotransmitter, go to lamina 1.
- IB4+: contains electin, not involved in the physiology, goes to lamina 2.
32
How did they decide on modern molecular definition of sensory neurons?
- They started by isolating 800 spinal cord cells
- They did single cell RNA-sequencing, they can count the amount of molecules of a specific genes that we're expressed in each neurons.
- Cells that have similar genes patterns are similar, they put them into categories (clustering)
33
What is neurogenic inflammation and how does it happen? (CRGP, substance P, plasma extravasion)
- efferent function of nociceptors
- inflammation that was caused to happen by neuronal activity
- When that neurons fires, 2 transmitters are released: CGRP and substance P, they dilate arteries really well.
- When that happens, there is plasma extravasation, the skin is gonna puff up, and it's gonna be inflammated.
34
What are spinal reflexes?
- A muscle action without involvement of the brain.
| - Up to spinal cord to decide whether reflex should be triggered.
35
What do ascending nociceptive pathways serve for?
- The info coming out of the second-order neurons, has to go to the cortex to be perceived.
- They travel up the white mater, either in the dorsal column or in the antero lateral column.
36
What are the 3 main ascending nociceptive pathways?
-spinothalamic tract: Spinal cord to thalamus, almost everything that is touch sensation goes to thalamus, touch or pain
-spinoreticular tract: spinal cord to reticular formation, specific to pain.
-spinoparabrachial: specific to pain, seems to be involved in the emotional side of pain.
goes form spinal cord to parabrachial, and from parabrachial to limbic system.
37
What is the use of somatotopy?
you can figure out which part of the body goes into which part of the cortex.
38
How is the trigmenial nerve constructed?
3 divisions:
- Ophtalmic (v1): eye area
- Maxillary (v2): nose area
- Mandibular (v3): mouth area
39
How is the visceral pain anatomy constructed?
- anatomy for visceral pain (organs) is slightly different
- most organs can feel some type of pain
- sometimes it goes right to dorsal rout ganglia
- but it often goes to other ganglia further from spinal cord to eventually end up in spinal cord
40
What is the difference between somatic and visceral termination?
- pattern of somatic termination: discrete, precise
| - pattern of visceral termination: more diffused and all over the place
41
What does the diffused termination of visceral pain explain?
-visceral pain is harder to localize (tummy vs finger)
42
What is somatic/visceral convergence and how can you explain it ?
Convergence explains the perceptual phenomenon of referral.
An afferent neuron that come from different locations can converge, and that is why sometimes when the pain is inside it feels like it's outside. Pain is referred to a somatic structure because of reference.
43
What is ischaemia?
lack of oxygen
44
What is distension?
pushing from the inside
45
Can muscle pain be referred?
Yes, muscle pain can refer as well, it can be refereed to muscle in another area, skin or visceral pain.
46
Who was the scientist who made the first description of referred pain?
James Mackenzie
47
What are the several ways of measuring electrical activity directly?
- electrophysiology
- EEG
- MEG
48
What are the 2 things you can measure with electrical activity?
- Metabolic response
| - Haemodynamic response
49
What does metabolic response measure?
- Neurons that fire more need more glucose and more oxygen.
| - So if you measure metabolic response, you can refer that there is more electrical activity.
50
What does haemodynamic response measure?
- rapid delivery of blood can activate neuronal tissues
| - if you measure blood flow, volume and oxygenation, you can infer electrical activity.
51
What is FMRI and why is it popular?
- measures oxygenation of parts of brain
| - more firing, more oxygenated blood being delivered.
52
How do you read an FMRI?
-The colours represent the evidence that a particular brain area responded to certain stimuli.
53
How was the pain matrix studied?
Studied the percentage of time scientist found the brain areas that compose the "pain matrix" were related to pain in non-pain patients.
54
What can we say about the pain matrix after studying it?
- pain matrix doesn't always refer to pain we want to study
- It doesn't seem directly related to pain
- pain matrix is only for acute thermal pain (no info on chronic pain)
55
What are the sensory-discriminative aspects of pain?
- localization of pain
- quality of pain
- intensity of pain
56
What are the motivation-affective aspects of pain?
- unpleasantness
| - meaning of pain
57
What did they do in 1997 study with hypnotization and the aspects of pain?
- gave hypnotic suggestions related to pain: pain should be less vs pain should be more, pain is pleasant/unpleasant
- suggestions related to intensity changes the s1 lighting up
- suggestions related to pleasantness changes AC lighting up.
58
What brain parts are responsible for the sensory-discriminative aspects?
-somatosensory cortex
59
What brain parts are responsible for the motivational-affective aspects? (6) (ainapv)
- anterior cingulate cortex
- insula
- nucleus accumbens
- amygdala
- parabrachial nucleus
- ventral tegmental area
60
What is the purpose of descending pain-modulatory pathways?
-Purpose is to send information back down to the spinal cord so that the info being passed up can be modulated.
61
What are the two systems o descending pain-modulatory pathways? (mlvs) (prds)
- midbrain-->locus coeruleus-->ventrodorsal funiculus-->spinal cord
- periaqueductal gray-->rostroventral medulla-->dorsolateral funiculus--> spinal cord.
62
What are the two main battles about pain physiology?
- specificity and intensity theory: Ed Perl
| - pattern theory and gate control theory: Ton Melzack and Pat Wall
63
What does Ed Perl defend in his specificity and intensity theories?
- specificity theory: says that there are nociceptors and their properties are that if the intensity is innocuous, the neuron will not fire, if it becomes noxious it can fire until a certain point.
- intensity theory: Maybe these nociceptors can also fire a little bit with touch stimuli.
64
What do Pat Wall and Ron Melzack defend in their pattern and gate control theories?
- pattern: According to this theory, there are no specific nerve fibers or endings used just for the sensation of pain. Instead, different sensations, such as cold, pain, heat, and touch, are detected by the same nerves, which then send specific signal patterns to the brain. The brain interprets the pattern, which includes both the sensation and its intensity, and the specific sensation is felt.
- gate control: the gate control theory of pain asserts that non-painful input closes the nerve "gates" to painful input, which prevents pain sensation from traveling to the central nervous system.
65
According to the gate theory what happens when a large neuron fires alone?
If large neuron fires alone it inhibits themself by inhibiting the sg (substantia gelatinosa) to fire them, so they don't fire
66
According to the gate control theory, what happens if only the small neurons fire?
If only small neurons fire, they are going to excite the transmission neuron to fire and they are going to inhibit the SG neuron from inhibiting so there is
no other way than firing.
67
How does the gate control theory explain why people rub where it hurts?
If you rub a part, you're getting small fiber input from pain and large fiber input from the rubbing. If they are simultaneously activated, either there is no pain at all, or there is less.
68
What can you record with microneurography?
- you can record primary afferent fibers in the foot, but it is very hard to do.
- You can only record in the leg because recordng C fibers in the spinal cord or brain would be very risky for the participant. No one wants to volunteer for that.
69
What is the purpose of doing electrophysiological recording of dorsal horn cells?
- find the dorsal horn cells that care about the foot
| - working on a foot can help measure what happens in the dorsal horn
70
What are the major dorsal horn projection neuron types? (WDR) (NS) (LTM)
-wide dynamic range (WDR): they response to a wide range of stimulus intensities (touch and pain) (Abeta, Adelta, C)
-nociceptive-specific (NS): only respond to Adelta and C.
-low-threshold mechanosensitive (LTM)
(“silent nociceptors”): only get input from Abeta. why are we talking about them? after injury, these neurons can now fire
71
What is CPM?
Refers to the diminution of perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals.
72
What is fibromyalgia?
Fibromyalgia is characterized by widespread pain and tenderness (sensitivity to touch).
73
What was the finding of the study on CPM with normals and fibromyalgics?
- Normals have pain before CPT and no more pain after CPT.
- Fibromyalgics have the same pain before and after, they don't have CPM. Condition modulation isn't working well, and maybe that's why they have fibromyalgia. CPM can be a predictor of who gets fibromyalgia.
74
What did they find in the study about CPM and drug efficacy?
There's a significant correlation between how good your CPM is and whether a particular drug (duloxetine) helps your pain. Those who's CPM work well, the drug didn't help, and vice-versa. Because people that have CPM don't need the drug, they're already using their CPM for pain relief.
75
How does TENS work (Transcutaneous Electrical Nerve Stimulation)
-Put electrode pads on part of your body that hurts, then it passes currents, just enough to stimulate the nerve fibers that are underneath the pads.
76
How does Gate Control Theory explain TENS?
It turns out that in nerve bundles containing primary afferent the Abeta tend to be closer to the epidermis and C fibers further down. It turns out that the TENS is giving just enough electrical stimulation to penetrate the skin through the epidermis and through the upper layer of the dermis but not further down. It's stimulating the Abeta but not C fibers. This is why TENS is analgesic (it stimulated the large fibers).
77
After an injury, are the injured fibers or uninjured fibers causing the pain?
Take the sciatic nerve that has 3 fibers: L4, L5, L6
It turns out that if you cut L5, some of the afferents in the sciatic nerve will start to degenerate because they're cut off from their cell body. Some of the fibers are gonna be dying and some of them are gonna be perfectly intact. Are the injured or uninjured fibers causing the pain?
Evidence that it is both.
78
What is the main difference between pain and other sensations in the environment?
Other sensations habituate, pain sensitizes.
79
What are the two places where sensitization can happen?
Two types of sensitization:
- peripheral: nerves endings out in the periphery can be sensitized and that can be caused by inflammation.
- central: spinal cord and brain
80
What is skin-nerve preparation ?
-Skin-nerve preparation: you ca get a sample of skin with intact nerves, you can stimulate the skin and record a single C fiber, and get it to fire.
81
What did they do in the study about peripheral sensitization by using skin-nerve preparation?
- show intracutaneous temperature before and after bradykinin
- bradykinin= substance that causes peripheral sensitization.
- Before the bk, the cells didn't start firing fast until you got up to 45degrees
- After bk, neurons are firing faster at lower temperatures
- So something has happened out in the periphery to make the primary afferents easier to fire and more often. Which is what happens in allodynia and hyperalgesia.
82
What did Clifford Woolf do in his research about central sensitization?
- rats given brain injury: more sensitive to pain for the next three hours
- on the contralateral side of the injury, after the injury, a neuron fires.
- This is due to changes in the central nervous system: central sensitization
83
What did alot of studies find about central vs peripheral sensitization?
- if there is peripheral sensitization, the primary neuron would fire more after the injury
- If you have central sensitization, and you are measuring the C fiber, you are not gonna see any change at all, because in absence of peripheral sensitization it's not gonna fire. But if you record in the spinal cord, you are going to see an increase.
84
What happens to peripheral and central sensitization in normal circumstances?
More likely to get both in normal circumstances.
85
What is spatial summation/wind-up?
- simple procedure: give pain stimuli, repeatedly close enough together.
- At every stimuli, there is more and more firing.
86
What was found in a study with back pain patients and spatial summation?
Maybe they have back pain because they have central sensitization, and if they have central sensitization they have spatial summation.
87
What was found on primary and secondary hyperalgesia and allodynia ?
- If they do a little burn on your skin, there are two zones: primary zone is precise site of injury, secondary zone is area around the injury.
- They observe the sensitivity.
- On the injury: both thermal and mechanical hyperalgesia and allodynia
- Surrounding the injury: only mechanical (area where LTM have turned into nociceptors)
88
What are the two types (areas) of secondary hyperalgesia?
- stroking hyperalgesia: dynamic hyperalgesia
| - punctate hyperalgesia+stroking: static hyperalgesia
89
Does analgesia or local desensitisation block secondary hyperalgesia?
No it doesn't
90
What is mirror pain?
Mirror pain, is pain experienced on both sides of the body, usually after trauma or inflammation in a limb on one side.
91
In what circumstances of stimulus and sens. do you get primary allodynia?
-If there is peripheral sensitization and no central sens. and you get an innocuous stimulus, you're gonna get primary allodynia, firing of Adelta and C
92
In what circumstances of stimulus and sens. do you get primary hyperalgesia?
-noxious stimulus, peripheral sensitization (no central), Adelta and C fire.
93
In what circumstances do you get secondary allodynia?
-innocuous stimulus, low threshold neuron firing (Abeta), central sensitization.
94
In what circumstances do you get secondary hyperalgesia?
noxious stimuli, nociceptor firing (Adelta or C), central sensitization.
95
In what circumstances do you get paresthesia?
ectopic activity (pain with no stimulus), firing of low threshold neuron (abeta), no central sens.
96
In what circumstances do you get spontaneous pain?
ectopic activity, nociceptor firing by itself (Adelta or C), no centra sens.
97
In what circumstances do you get dysesthesia and spontaneous pain?
ectopic activity, low threshold neuron firing by itself, central sensitization.
98
Functional plasticity: What happens during molecular changes?
-molecular changes: after injury (ex: heat stimulus), inflammation, ion channel sensitization, even with a lower heat stimulus, the ion channel is letting more calcium in than before. This could ultimately result in allodynia or hyperalgesia.
99
Functional plasticity: what is synaptic change?
-more transmitter release, more receptors, so more pain transmission
100
Functional plasticity: what is cellular change?
- more likelihood for a neuron to fire (more excitability)
| - after injury, the receptive fields of a dorsal horn neuron gets bigger, so more likely to fire and spatial summation.
101
Functional plasticity: what are network changes?
-after inflammation, more neurons respond to stimulus.
102
Three types of structural plasticity after injury?
-more synaptic spines, more transmission
-connectivity: in some pain conditions you can find more branching patterns (at nerve endings). This is called hypertrophy and sprouting.
Also work the other way: nerve damage, less branching pattern, called denervation. (leads to numbness and pain)
-cell number: can grow more neurons, would probably cause more pain.
103
What did they find about ectopic firing and spontaneous pain i a study with rats?
- rats: normal and diabetic. looking at responses of primary afferents.
- in the diabetic rat: the receptive field gets bigger, allodynia, hyperalgesia, spontaneous pain.
104
What happens to microglia after injury?
-after injury they undergo microgliosis: they become activated, release new things, which changes the other cells.
