L4 - Sensory Neuropathies

Question 1

What is nociception?

Answer 1

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

Question 2

Where are the cell bodies of nociceptive neurons found?

Answer 2

Dorsal root ganglion (DRG)

Question 3

What is the circuitry from the DRG?

Answer 3

Primary sensory neurons in DRG project dendrites to peripheral tissue

Question 4

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

Answer 4

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

Question 5

What are the features of Adelta fibres?

Answer 5

Cause immediate response
Mechanosensitive and mechanothermal
Large diameter

Question 6

What happens at the dorsal horn?

Answer 6

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

Question 7

Where can modulation of the signal occur?

Answer 7

At high levels of comms between 2nd order neurons

Feed through descending inhibitory pathways

Question 8

What does the amygdala do?

Answer 8

Processes info relevant to aversive properties of pain

Question 9

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

Answer 9

Enkephalin

Question 10

What does enkephalin do?

Answer 10

Inhibits release of glutamate and substance P

Question 11

What does the inflammatory soup do?

Answer 11

Released in reponse to damage

Potentiate or maintain initial nociceptive signal

Question 12

What are part of the inflammatory soup?

Answer 12

Protons, ATP, NTs alter neuronal excitability directly

Bradykinin, NGF bind to metabotropic receptors (longer signal)

Question 13

What is a hallmark physiological response to injury?

Answer 13

Tissue acidosis

Question 14

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

Answer 14

Act to inhibit TRPV activation

Capsaicin, olvanil, anandamide

Question 15

What is hyperalgesia?

Answer 15

Resducing threshold for stimulation

Question 16

How is nociception modulated?

Answer 16

Modification of TRPV1 to lower threshold activation

Question 17

What does damage to nociceptor neurons lead to?

Answer 17

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

Question 18

Why does damage to neurons lead to ectopic activation?

Answer 18

Long term activity results in long term changes

Question 19

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

Answer 19

Activity dependent central sensitisation

Txn dependent central sensitisation

Question 20

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

Answer 20

Cox2 induction

Question 21

What is DREAM?

Answer 21

Inhibitory TF in the dorsal horn neuron nucleus

Question 22

What is sprouting?

Answer 22

Activity can lead to nerve sprouting

Ectopic connections onto other circuits

Question 23

What is excitotoxic shock?

Answer 23

Too much activity can kill a neuron leading to disinhibition

Question 24

What is neuralgia?

Answer 24

Pain in distribution of nerve or nerves

Question 25

What is neuropathy?

Answer 25

Disturbance of function in nerves

Question 26

What is neuritis?

Answer 26

Special type of neuropathy with inflammatory process

Question 27

What is allodynia?

Answer 27

Condition where normally non-painful stimuli become painful

Question 28

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

Answer 28

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

Question 29

What are the two types of CMT disease>

Answer 29

CMT type 1 - demyelinating disease

CMT type 2 - diminished responses in sensory neurons

Question 30

What can the loss of the myelin sheath cause?

Answer 30

Reduced transmission

Spontaneous production of action potentials

Question 31

What can demylination lead to?

Answer 31

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

Question 32

Why does demyelination lead to excessive metabolic demand?

Answer 32

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

Question 33

What is the cascade of CMT pathology?

Answer 33

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

Question 34

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

Answer 34

GDAP1
mitofusin2
dynamin related protein 2

Question 35

How does fusion of mitochondria occur?

Answer 35

Mfn’s(GTPases) mediate tethering of pre-fusogenic mito

OPA1 on inner membrane (dominant mutation in domiant optic atrophy)

Question 36

How does fission of mitochondria cocur?

Answer 36

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

Question 37

What 2 bad things can happen to mitochondria ?

Answer 37

Heterogeneity in pop, some with poor function

Mitochondrial aggregation

Question 38

What is HSAN1 and what are its features?

Answer 38

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

Question 39

What neurological diseases are associated with sphingolipid metabolism?

Answer 39

HSAN1
Bovine spinal muscular atrophy
LSDs

Question 40

what is SPTLC1?

Answer 40

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

Question 41

You should look at the last few slides of this lecture

Answer 41

do it mate, remember cancer and cell cycle