Lecture 3 Flashcards
Pain Anatomy and Physiology
1
Q
What was the first person to develop the concept of pain pathways?
A
Rene Descartes in 1644.
2
Q
What is stress-induced analgesia?
A
When the brain doesn’t want to know something and prevents itself from hearing it (descending modulation)
3
Q
What is the periphery?
A
Things outside the nervous system (i.e. the skin, muscles, joints, and viscera).
4
Q
What is a pain pathway?
A
Information is passed through the periphery to the dorsal root ganglion to the dorsal horn of the spinal cord to the brain.
5
Q
What is contained in the ‘pain matrix’?
A
The thalamus, the somatosensory cortex, the limbic cortex (the insula and anterior cingulate cortexes specifically), the basal ganglia, the prefrontal cortex, etc.
6
Q
What is a descending pathway?
A
Information goes from the hypothalamus to the midbrain to the brainstem to the spinal cord.
7
Q
What are the two types of skin?
A
Glabrous and hairy.
8
Q
What are free nerve endings?
A
Where the nerve just starts or stops.
9
Q
What are nociceptors?
A
A sensory nerve fibre called an afferent fibre. They are responsive to noxious stimuli. They are unipolar. The dendrites are the free nerve endings in the skin, joints, muscles and viscera. The axons are the end of the central processes in the spinal cord. The cell body is the DRG.
10
Q
What does afferent mean?
A
Going up towards the brain.
11
Q
What are muscle control fibres?
A
A nerve fibre called an efferent fibre (from brain to muscles).
12
Q
What are the four types of afferent fibres and what are they for?
A
A-alpha (proprioception or muscle control) - these are the biggest and conduct the fastest
A-beta (touch and vibration)
A-delta (thermal and pain)
C (pain and sweating) - these are the thinnest and conduct the slowest
13
Q
What are the two waves of pain?
A
A sharper, more immediate pain that subsides quickly - A-deltas are responsible for this pain.
A duller, and longer lasting pain that takes a second or two to start - Cs are responsible for this pain.
14
Q
What is the endoneurium?
A
The filler tissue in between each axon.
15
Q
What is the perineum?
A
The larger structures separating the pockets of axons.
16
Q
What are the four different sections of the spinal cord?
A
Cervical (8 spinal nerves)
Thoracic (12 spinal nerves)
Lumbar (5 spinal nerves)
Sacral (5 spinal nerves)
17
Q
What are dermatones?
A
Parts of the body or skin that a spinal nerve serves.
18
Q
What do ipsilateral and contralateral mean?
A
Ipsilateral is on the same side as the noxious stimulus. Contralateral is the side opposite from the noxious stimulus.
19
Q
Where are the bulbous and tri-horned bones in the spinal column located?
A
The bulbous bone is on the ventral side (facing the tummy) and the tri-horned bone is on the dorsal side (facing the back)
20
Q
Are anterior or posterior horns bigger?
A
Anterior or ventricle horns are bigger than posterior or dorsal horns.
21
Q
What are meninges?
A
Dura matter on the outside, arachnoid matter in the middle, and pia matter on the inside.
22
Q
What is white matter?
A
White matter is axons, nerve fibres going either in or out. It is white because most of the axons are myelinated.
23
Q
What is gray matter?
A
Neurons
24
Q
What are the big neurons in the ventral horn and what do they do?
A
Motor neurons. The cell bodies of the motor neurons go out of the ventral root into the mixed spinal nerve and travel down to whatever muscle or plate they’re controlling to produce movement.
25
What is another name for spinal cord laminae?
Rexed's laminae.
26
How many laminae are on the dorsal horn and how many are on the ventral horn?
6 laminae on the dorsal horn and 4 laminae on the ventral horn.
27
What is outside of lamina 1?
Lamina 1is the closest to the outside (or dorsal side) of the spinal column. the space outside of lamina one is the dorsolateral fasciculus. There are no cell bodies here.
28
What is another word for Laminas 1 and 2?
The substantia gelatinosa
29
How is pain stimulus sent up to the brain through the spinal cord?
The nociceptor (primary afferent) fires first and sends the information to the dorsal ganglion. The dorsal ganglion sends the information through the dorsolateral fasciculus into the spinal cord. It then goes to the substantia gelatinosa and either synapses on second-order neurons, crosses the midline, gets into the white matter and starts going up to the brain OR it synapses on second-order neurons that project to the deeper lamina of the spinal cord, sends the information to a third-order neuron which then crosses sides and goes up to the brain.
30
What are the two ways information can be sent to the brain?
Either the spinal cord just passes information to the brain, or there's additional processing inside the spinal cord before the information gets sent up.
31
What is a peptidergic C fibre? Where does it terminate?
A C fibre that contains a peptide (small proteins) neurotransmitter. They terminate superficially in lamina 1.
32
Where do non-peptidergic C fibres terminate?
Deeper in lamina 2.
33
Where do A-delta fibres go to?
Both lamina 1 and 5.
34
What are the two types of C fibres?
Peptidergic and IB4.
35
What are the the two peptides in peptidergic C fibres?
CGRP (calcitonin gene-related peptide) and substance P.
36
What is single-cell sequencing?
A technique where you can sequence a particular cell to determine how many copies of a certain gene exist. It looks at gene expression.
37
How many primary categories are there for primary afferent fibres?
11
38
How many neurons are there?
622
39
How many neurofilament heavy chain expressing (NF) neurons are there?
139
- NF1 has 31
- NF2 has 48
- NF3 has 12
- NF4 has 22
- NF5 has 26
40
How many non-peptidergic (NP) neurons are there?
169
- NP1 has 125
- NP2 has 32
- NP3 has 12
41
How many peptidergic (PEP) neurons are there?
81
- PEP1 has 64
- PEP2 has 17
42
How many tyrosie hydrolase-expressing (TH) neurons are there?
233
43
What is an axon reflex?
When the action potential, in addition to going up, also turns a corner and causes the release of whatever transmitters are in those nerve terminals.
44
What do peptidergic C fibre peptides do?
They cause vasodilation - they make your blood vessels bigger and leaky which causes swelling and inflammation. They also cause the infiltration of immune cells which causes swelling and inflammation.
45
What does vasodilation do?
When your blood vessels get bigger and leaky, one of the substances released is plasma. When plasma is released into the tissue surrounding those arteries, the tissue becomes inflamed and swollen.
46
What is the longer way for your body to escape a noxious stimulus.
A-delta sends info to your spinal cord, your spinal cord processes it and sends it to your brain, there is pain perception, your brain generates a motor plan, the motor cortex sends that info to the spinal cord, the spinal cord sends that info to the motor neurons, and the motor neurons send that info to the muscle which generates a movement away from the noxious stimulus.
47
What is the spinal reflex?
The quickest way for your body to escape a noxious stimulus. One interneuron goes from the dorsal horn to the ventral horn which activates the motor neurons directly and generates a movement away from the noxious stimulus.
47
What are the two different routes information can take after getting into the white matter?
It can either go up the dorsal column or the anterolateral column.
48
What are the the three ways information can get to the cortex?
The spinothalamic tract which goes from the spinal cord to the thalamus (this is for sensory information).
The spinoparabrachial tract that goes from the spinal cord to the parabrachial in the pons and ends up in the limbic system (this is for emotional information).
The spinoreticular tract which goes from the spinal cord to the reticulum in the midbrain (this is for basic automatic nervous system functions).
49
What is somatotopy?
The concept that everything is organized by body site.
50
What are the three subdivisions of trigeminal nerves?
V1, V2, and V3, all of which have dermatomes.
51
How does pain from above the neck make it to the brain?
Information is sent into the trigeminal nerves through A-delta and C fibres in the trigeminal spinal tract; the information is then sent to the trigeminal ganglions, which then project centrally.
52
What is the vagus nerve?
A nerve that passes information directly to the brain, bypassing the spinal cord entirely, and ends up in the nucleus tractus solitarius.
53
Why is visceral pain harder to localize than somatic pain?
Because when information is sent into the spinal cord, it's all over the place rather than the discreet way somatic sensory information is.
54
Why is visceral pain localized to somatic structures?
Information coming from the viscera terminates on the same second-order neurons as somatic information.
55
What are somatic stimuli?
Mechanical, thermal, and inflammatory stimuli.
56
What are visceral stimuli?
Ischemia (restriction of blood supply), distension, and inflammatory stimuli.
57
What is the percentage of the saline inside of your body?
0.9%
58
Who conducted the first study on referred pain and when was it?
James Mackenzie in 1909.
59
What are the three ways to do brain mapping?
Through lesions, stimulation and recordings, or hemodynamic response.
60
What are some examples of lesions that can be used to brain map?
Natural - disease or trauma
Induced - TMS (transcutaneous magnetic stimulation) or surgery
61
What are some examples of stimulation and recordings that can be used to brain map?
Direct - electrodes or optical imaging
Indirect - EEG (electroencephalography), ERP (event-related potentials), or MEG (magnetoencephalography)
62
What is the best way to map the brain?
Hemodynamic response
63
What does hemodynamic response do and what are some examples of it?
Hemodynamic response measures the proxy of neuronal activity by seeing that if the brain is more hardworking, more neurons will fire and take more oxygen out of the blood supply.
PET - positron emission tomography
SPECT - single-photon emission computerized tomography
fMRI - functional magnetic resonance imaging
64
What is the most common brain mapping technique?
fMRI
65
What are some aspects of sensory-discriminative pain?
It can be localized, you can tell the quality of the pain (sharp vs. dull), and you can tell the intensity of the pain. This is connected to the somatosensory cortex and comes from the spinothalamic tract.
66
What are some aspects of motivational-affective pain?
You can tell its unpleasantness, and there is a drive to escape or attend to the pain. This is connected to the anterior cingular cortex (ACC) and comes fro the spinoparabrachial tract.
67
What is pain asymbolia?
When people admit that they have pain and can tell you the intensity of it, but do not have the emotional response to pain anymore.
This is due to lesions of the insula, cingulate or morphine
68
What are the two circuits for descending pathways from the midbrain to the spinal cord?
The first goes from the PAG (periaqueductal gray) of the midbrain, to the RVM (rostroventral medulla), to the DLF (dorsolateral funiculus), to the spinal cord.
The other goes from the PAG of the midbrain, to the LC (locus coeruleus) of the pons, to the VLF (ventrolateral funiculus) to the spinal cord.
Once in the spinal cord information sent through either circuit will synapse onto the second-order projection neurons that would otherwise send a message up and stop them from firing.
69
What was Ed Perl's theory on pain physiology?
The Specificity Theory.
70
What was Pat Wall and Ron Melzack's theory on pain physiology?
The Gate Control Theory.
71
Who discovered nociceptors?
Ed Perl
72
What is the Specificity Theory?
Nociceptors do not fire for innocuous stimuli; only a when a stimulus becomes noxious does that primary afferent fire occur. The more noxious a stimulus is the, the more the primary afferent fibres will fire.
When a noxious stimulus does occur and the nociceptors fire, the pathway is through the skin, to the DRG nociceptors, to the dorsal horn nociceptive neurons.
73
What is the Intensity Theory?
Innocuous stimuli can also make primary afferent neurons fire. The more noxious a stimulus gets, the more the neurons will fire.
The pathway for both noxious and innocuous stimuli is through the skin, to low threshold DRG neurons, to WDR dorsal horn projection neurons.
74
What is the Pattern Theory?
Both noxious and innocuous stimuli activate several types of primary afferents and they all have different firing patterns which is figured out in the spinal cord. Those patterns are how we figure out if something is pain or not, and if it is, how much.
75
When was the Gate Control Theory first proposed and in which journal?
In 1965 in the journal Science.
76
What are the two input types in the Gate Control Theory?
Large fibres (A-betas) and small fibres (A-deltas, and Cs)
77
What is the Gate Control Theory?
Touch information from A-betas and pain information from A-deltas and Cs comes in and go directly to the T-neuron and excite it. The more the T-neuron fires, the more pain will be perceived. The smaller SG neuron can inhibit input from the fibres to the T-neuron. The more the SG neuron fires, the less the fibres will be able to excite the T-neuron, and the less pain will be perceived.
When large fibres reach the SG neuron, they excite it, causing the SG neuron to fire which prevents information from reaching the T-neuron.
When small fibres reach the SG neuron, they inhibit it, causing the SG neuron not to fire, and allowing information to reach the T-neuron.
If the T-neuron fires, the gate is open, and you get pain. If the T-neuron is prevented from firing from large fibre input or central control, the gate is closed, and you get less or no pain.
78
What is microneurography?
When you poke a recording electrode into the foot and directly record C fibres or A-deltas.
79
What are the three types of dorsal horn/second-order/projection neurons in the dorsal horn?
Nociceptive-specific neuron: it only has A-deltas and Cs, and there is no beta input.
Wide dynamic range neuron: it has input from A-deltas, A-betas, and Cs. It responds to both innocuous and noxious stimuli.
Low-threshold mechanosensitive neuron: they only respond to mechanical stimuli. They are also called silent nociceptors, as they are silent before an injury and only begin to do stuff after one occurs.
80
What is the receptive field on an anterior cingulate?
Most of the body or the whole body.
81
What is counterirritation?
The idea that pain in one place can inhibit pain in another place. By getting punched in the arm really hard, your knee might stop hurting.
82
What is conditioned pain modulation (CPM)?
Another word for counterirritation; this is what most people call it. More CPM in your descending modulatory system means they are working better, whereas less CPM means they are not working very well. Inefficient CPM might be the cause of chronic pain.
83
What is Transcutaneous Electrical Nerve Stimulation (TENS)?
The placement of electrodes on your skin in the general location of the pain. They pass currents from the anode to the cathode to make the neurons under or in between the electrode fire action potentials.
84
What causes phantom limb pain?
If all the nerve fibres that take information from one part of the body to the brain are severed, it produces phantom limb pain (i.e. amputation).
85
What do degenerating nerve fibres do?
They can produce pain from their absence, but release factors that change the uninjured nerve fibres so that something is added to their function to produce pain.
86
What are the two types of sensitization?
Peripheral (which is neurochemical) and central (which occurs in the central nervous system).
87
What is skin-nerve preparation?
When you take a piece of skin from an animal while it's still alive, and tease out a nerve fibre that would have been running from the skin to the DRG and spinal cord and put it in a bath to keep it alive and record from it.
88
Who discovered central sensitization? When? What paper was it published in? What did they do?
Clifford Woolf discovered central sensitization in a sole-authored study published in 1983 in a paper called Nature.
He applied a heat stimulus to rats the measure the lowest amount of mechanical stimulus in grams it would take for the rat to try and withdraw from it. He measured this using second-order neurons in the spinal cord. After the injury, the rats were extremely allodynic for about 5 hours. The neurons were firing on the contralateral side, which would only be explained if the second-order neurons themselves had changed such that a stimulus that would normally not be painful became painful after the injury. The second-order neurons had changed their properties such that normal stimulation of intact, non-injured skin on the other side of the body was making the neurons fire as well.
89
What does electrophysiological recording do?
It can distinguish between peripheral and central sensitization.
90
How can you tell if there's only peripheral sensitization?
Regardless of where you're electrophysiologically recording from, you will see a certain amount of firing from before the injury and more firing after the injury. You will see the same thing in the CNS. In peripheral sensitization, the nociceptor will be activated more.
91
How can you tell if there's only central sensitization?
You wouldn't see any change in the periphery, but there will be more firing in the spinal cord. In central sensitization the spinal cord neuron has changed.
92
What is temporal summation or the 'wind-up effect'?
When you give a pain stimulus in one-second intervals (for example), as the more times you give the stimulus, the more the neurons will fire. If the stimuli's intervals are far apart, they will not produce temporal summation and it will simply be a stimulus. But, if the stimuli are close enough to summate with each other, the pain ratings will get higher and higher the more you give the stimulus. Temporal summation is evidence that central sensitization has occurred.
93
What is primary hyperalgesia?
The things that happens close to or at the site of the injury.
94
What is secondary hyperalgesia?
It is mechanically specific and doesn't work with heat stimuli. It is what happens further away from the site of the injury in uninjured tissue.
95
What are the two types of secondary hyperalgesia?
Punctate hyperalgesia and stroking hyperalgesia. By using stroking stimuli, the secondary hyperalgesia doesn't go as far as if you use punctate stimuli.
96
What is ectopic firing?
When afferents fire by themselves with no peripheral input. If a nociceptor fires ectopic activity, that is spontaneous pain.
97
What is functional plasticity?
When whatever is there changes its function to produce sensitization. There are molecular, synaptic, cellular, and network changes. Nothing has to be made or removed, there is simply a change in configuration.
98
What is structural plasticity?
When new things are being made or removed; some physical change has occurred. You can change the number of synaptic spines you have, the connectivity of your axons (denervation or hypotrophy), and the number of cells you have.
