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Clinical Neurobiology > Somatosensory & pain > Flashcards

Somatosensory & pain Flashcards

1
Q

The 3 skin layers

A

Epidermis, dermis & hypodermis

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2
Q

Where are our touch receptors?

A

In the dermis (some close to the epidermis)

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3
Q

4 types of touch receptors and their placement

A

Merkel disk receptors(between epidermis and dermis)
Meissner corpuscles(between epidermis and dermis)
Ruffini endings(in dermis)
Pacinian corpuscles(in dermis

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4
Q

How do you determine the receptive field for the touch receptors?

A

2-point discrimination test

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5
Q

Devide the 4 touch receptors by deep/superficial layering and by rapid/slowly adabting

A

Merkel disk receptors(superficial and slow)
Meissner corpuscles(superficial and fast)
Ruffini endings(deep and slow)
Pacinian corpuscles(deep and fast)

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6
Q

Which touch receptors code for surface contour?

A 
superficial receptors (Merkel disk receptors and 
Meissner corpuscles)
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7
Q

4 types of information yielding sensation

A
  1. Modality = receptor type
  2. Localization (where it is and the extension of the receptive field)
  3. Adaptation (duration of the stimulus)
  4. Timing = combination of AP frequency and duration of the nerve impulse.
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8
Q

The diameter of a probe is coded by which receptor?

A

Merkel disc receptors

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9
Q

Which receptors have “air-bags”?

A

Meissner and Pacinian receptors (rapidly adabting)

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10
Q

What are temperature receptors called?

A

transient receptor potentials (TRPs)

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11
Q

Which temperature receptors open for “drugs” and which “drugs” are these?

A

TRPM8 opens at ~20°C and in the presence of Menthol. TRPV1 opens at ~40°C and in the presence of Capsaicin

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12
Q

Rapid/slow adaptors in the temperature system

A

rapid = warm, cold = slow - cold water is cold for a long time, but hot water becomes “normal” quickly

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13
Q

How is proprioception mediated?

A

By muscle spindle receptors and the golgi tendon organ (detects stretch and contractions respectively)

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14
Q

IA afferent nerve fiber

A

IA afferent nerve fiber is the sensory fiber of a stretch receptor found in muscles called the muscle spindle, which constantly monitors how fast a muscle stretch changes. (In other words, it monitors the velocity of the stretch).
IA afferent fibers transfer the information about muscle length and tension to alpha and gamma motoneurons in the spinal cord. Alpha motoneurons project back to the skeletal muscle whereas gamma motoneurons project to the muscle spindle

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15
Q

IB afferent nerve fiber

A

IB afferent neuron is associated with the Golgi tendon organ. These afferent fibers branch extensively and wrap around the many collagen fibers that compose the Golgi tendon organ and detects contraction.
To avoid an over-contraction of the skeletal muscle IB fibers send the information from the Golgi Tendon Organ to inhibitory neurons in the spinal cord to mediate muscle relaxation.

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16
Q

What fiber types carry what information?

A

A-alpha: proprioception
A-beta: touch
A-gamma: pain/temperature
C-fibers: pain/temperature

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17
Q

What’s a dermatome?

A

An area of skin whose sensory receptors responds to one spinal column

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18
Q

How does the dorsal medial lemniscus pathway go?

A

For proprioception and touch: information from A-alpha or A-beta fibers enter the spinal cord at Laminae IV (column of Clark) and is sent ipsilaterally through the Gracile/cuneate fasciculus to the medulla (in the Gracile or cuneate nucleus - where the lower motor neuron is) where it switches over to the medial lemniscus on the contralateral side. Here it goes through the thalamus (VPL) to the somatosensory cortex

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19
Q

How is the somatosensory cortex divided up?

A

from 2-1-3b-3a (from posterior to anterior). It shows a cortical somatotopy especially of area 3b. Area 3a get most of proprioceptive input; whereas area 1 and 2 are most important for the quality of the stimulus.

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20
Q

Lateral inhibition

A

lateral inhibition is when the surrounding neurons of a super-firing neuron are inhibited in order for one to find out where the signal from the super firing neuron is coming from

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21
Q

Subcategories of persistent pain

A

1) nociceptive (somatic or visceral) and 2) neuropathic (direct nerve damage)

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22
Q

The 3 major classes of nociceptive pain

A

Three major classes: thermal, mechanical, polymodal

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23
Q

Characterise thermal nociceptors

A

Responds to extrem temperature, have small diameter, are thiny myelinated (C and Aδ fibers), have slow conductance.

24
Q

Characterise mechanical nociceptors

A

For intensive pressure, conducted by Aß fibers, has faster conductance.

25
Characterise polymodal nociceptors
Are both mechanical and thermal, responds to chemical insults, has slow and fast conductance.
26
Describe first and second pain
First (quick and acute) and second pain (Slow, persistent and dull) are carried by two different primary fibers. First pain is carried by A-delta and secondary by C-fibers
27
Describe the spinothalamic tract (anterolateral system) 
Signal is sent to the Lamina I and II (Substantia gelatinosa). Here a secondary neuron sends the signal over contralaterally (glutamate is responsible) --> signal travels up through the thalamus (VPL) and into the somatosensory cortex
28
Why can visceral pain sometimes be felt as somatic pain?
To the the convergence of the two's afferent fibers
29
What causes hyperalgesia
Substance P causes vasodilation and secondary hyperalgesia (sensitization) COX can derive Archidonic acid to prostaglandine, which is the main factor of hyperalgesia, as it increases the sensibility of nociceptors
30
Bradykinins
direct activation of Ad and C fibers via increased ion conductance. It increases the prostaglandine synthesis., which makes it play a role in hyperalgesia
31
Prostaglandine
main factor of peripheral hyperalgesia, formed from damaged cells from Archidonic acid vis COX. It increases sensibility of nociceptors for other stimuli
32
What does aspirin block?
COX
33
Explain the gate theory of pain
When a stimulus is painful, the c-fibers send a signal to their secondary sensory neuron in the substancia gelatinosa. But, if there also is a touch sensation in the same area, the dorsal medial lemniscus pathway can cause an inhibitory neuron to inhibit the signal coming from the secondary neuron (thereby decreasing pain)
34
How does endorphins decrease pain?
Endorphins bind to their relevant receptors by activating a G-protein. This in turn blocks a voltage-gated Ca2+ channel and therefore reduces glutamate release in the spinal cord. The glutamate signal in the spinal cord is necessary for the anterolateral pathway.
35
Three classes of opioid peptides
Enkephaline, ß-Endorphine, Dynorphine
36
How does morphine work?
Morphine mimick endogenous opioids by block Glutamate release and thus the postsynaptic hyperpolarization in the 2nd order pain-related neuons
37
from 46000 people in 16 European countries how many percent suffer from chronic pain?
Nearly 19%
38
NGF and the anterolateral system
65% of all receptors are TrkA (for NGF). NGF1 is released from the skin. After binding to its receptor, NGF is transported to the soma in the dorsal root ganglia. There NGF1 support cell survival and differentiation. NGF1 up-regulates all factors mediating hyperalgesia and down-regulating it leads to decrease pain.
39
NGF regulates the expression of:
``` TRPV1 Bradykinin opiate receptors, Nav1.3-1.7-1.8-1.9 Substance P Prostaglandines ```
40
New treatments on pain?
Decreasing NGF
41
When TrkA leaves the cell after being created, it passes which cell-components for modifications?
The ER and the golgi complex
42
ER modifications of TrkA
Disulfid bonds, Glykosylation (the covalent addition of sugar moieties to specific amino acids), Connecting with Glykolipides
43
trans-Golgi modifications of TrkA
Glykosylation (N- u. O-) Phosphorylation Sulfation The modified proteins leave the golgi network by constitutive or induced secretion
44
Axonal Transport
The vesicles are bound to the microtubules via the motor proteins. Motor proteins are microtubules-associate proteins. They are ATPases and use ATP of the binding to microtubules. The transport is high energy.
45
Classes of motor proteins
kinesine for anterograde and dynein-complex for retrograde transport
46
Sortilin
Sortilin is a motor protein for TrkA and helps TrkA’s axonal transport on the microtubials
47
Knocking out sortilin in combination with P75 causes
leads to depletion of TrkB (less axons in the sciatic nerve, less touch perception); to depletion of TrkC (less muscle spindles); to depletion of TrkA (less pain perception) Animals start to self-mutilate --> can't feel pain
48
Von Frey test
plastic filaments are applied to the surface of the hind paw. The application evokes a hind-paw withdraw. You can determine the threshold of a WT/knockout mouse depending on stiffness of the filament
49
Hargreave test
Measure response to heat applied to the hind paw
50
which growth factors are upregulated in diabetic patients and why is that of our interst?
IGFBP5 an IGF1 - because many diabetics develop neuropathy where peripheral sensory- , motor- and autonomic nerve fibers are affected in number and function. Here we also see hypoalgesia, which could implicate these growth factors in a decreased pain perception
51
How does Igfbp5 transgenic mice score on the Von Frey and Hargreave tests?
They show decreased sensitively in both tests (could be indicatory of decrease pain-sensitivity)
52
What fibers are Igfbp5 transgenic mice missing?
Free nerve endings
53
Important sodium channels for pain?
Nav1.7, Nav1.8 and Nav1.9
54
Mutations in NaV1.7 can lead to?
The inability to feel pain
55
Mutations in NaV1.9 can lead to?
``` painful neuropathy (Hyperalgesia) NaV1.9 mutations has also been found to cause Increased AP firing to stimuli, Altered channel gating properties: Increased excitability and a reduced threshold for action potential firing ```
56
NaV1.8 mutations can lead to?
increased noiceception signalling in the cold
57
Treatment strategies against pain
Conventional: Prostglandine Blocker, opioid derivates. Human antibodies against NGF New potential targets: TrK receptors, Nav1.7, 1.8, 1.9, IGF-binding proteins

Clinical Neurobiology (9 decks)

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