L4 - Sensory Neuropathies Flashcards Preview

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Flashcards in L4 - Sensory Neuropathies Deck (41):
1

What is nociception?

Transduction of noxious stimuli and also cognitive and emotional processing of it

2

Where are the cell bodies of nociceptive neurons found?

Dorsal root ganglion (DRG)

3

What is the circuitry from the DRG?

Primary sensory neurons in DRG project dendrites to peripheral tissue

4

What are the main types of dendrites of these neurons and what receptors do they both express?

C fibres (slow)
Adelta fibres (fast and myelinated)

5

What are the features of Adelta fibres?

Cause immediate response
Mechanosensitive and mechanothermal
Large diameter

6

What happens at the dorsal horn?

Major input to CNS
Second order processing
Immediate response
Modulation of signal

7

Where can modulation of the signal occur?

At high levels of comms between 2nd order neurons
Feed through descending inhibitory pathways

8

What does the amygdala do?

Processes info relevant to aversive properties of pain

9

What kind of receptors are on the presynapse of nociceptive neurons?

Enkephalin

10

What does enkephalin do?

Inhibits release of glutamate and substance P

11

What does the inflammatory soup do?

Released in reponse to damage
Potentiate or maintain initial nociceptive signal

12

What are part of the inflammatory soup?

Protons, ATP, NTs alter neuronal excitability directly
Bradykinin, NGF bind to metabotropic receptors (longer signal)

13

What is a hallmark physiological response to injury?

Tissue acidosis

14

What do endogenous vanilloids generally do and what are some exampkes?

Act to inhibit TRPV activation
Capsaicin, olvanil, anandamide

15

What is hyperalgesia?

Resducing threshold for stimulation

16

How is nociception modulated?

Modification of TRPV1 to lower threshold activation

17

What does damage to nociceptor neurons lead to?

Increase in Na and reduction of K channels resulting in ectopic activation

18

Why does damage to neurons lead to ectopic activation?

Long term activity results in long term changes

19

What two things is sensory integration in the dorsal horn subject to?

Activity dependent central sensitisation
Txn dependent central sensitisation

20

What protein acts to reduce inhibitory input in txn dependent central sensitisation of the dorsal honr?

Cox2 induction

21

What is DREAM?

Inhibitory TF in the dorsal horn neuron nucleus

22

What is sprouting?

Activity can lead to nerve sprouting
Ectopic connections onto other circuits

23

What is excitotoxic shock?

Too much activity can kill a neuron leading to disinhibition

24

What is neuralgia?

Pain in distribution of nerve or nerves

25

What is neuropathy?

Disturbance of function in nerves

26

What is neuritis?

Special type of neuropathy with inflammatory process

27

What is allodynia?

Condition where normally non-painful stimuli become painful

28

What are the features of Charcot-Marie-Tooth (CMT) disease?

2.6m affected
Nerves to extremmeites degenerate with muscle weakness
no cure
18 types identified by genetics

29

What are the two types of CMT disease>

CMT type 1 - demyelinating disease
CMT type 2 - diminished responses in sensory neurons

30

What can the loss of the myelin sheath cause?

Reduced transmission
Spontaneous production of action potentials

31

What can demylination lead to?

Mitochondrial fission/fusion (enlarged mito seen in many forms of neuropathy)

32

Why does demyelination lead to excessive metabolic demand?

Whole axon requires ATP for pumps instead of just nodes of Ranvier

33

What is the cascade of CMT pathology?

Schwann cells myelinate poorly
Fail to support axons
Axonal transport defects
Progressive axonal loss
Muscle denervation and sensory losses

34

What are some mitochondrial fission/fusion related genes prevalent in neuropathies?

GDAP1
mitofusin2
dynamin related protein 2

35

How does fusion of mitochondria occur?

Mfn's(GTPases) mediate tethering of pre-fusogenic mito
OPA1 on inner membrane (dominant mutation in domiant optic atrophy)

36

How does fission of mitochondria cocur?

Fis1 covers outer membrane
Drp coalesces in spots of constriction
GDAP1 promotes fission

37

What 2 bad things can happen to mitochondria ?

Heterogeneity in pop, some with poor function
Mitochondrial aggregation

38

What is HSAN1 and what are its features?

-Hereditary, sensory, autonomic neuropathy type 1
- Distal sensory loss, sweating, slow healing wounds, amputation of legs
Mutations in SPT1LC1 and Rab7

39

What neurological diseases are associated with sphingolipid metabolism?

HSAN1
Bovine spinal muscular atrophy
LSDs

40

what is SPTLC1?

Subunit of serine palmitoyl-transferase enzyme - an enzyme involved in the de nova synthesis of sphingolipids

41

You should look at the last few slides of this lecture

do it mate, remember cancer and cell cycle