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Pain > B. Neuronal Pain Pathway > Flashcards

B. Neuronal Pain Pathway Flashcards

1
Q

What is the definition of pain (IASP definition)?

A

Unpleasant sensory and emotional experience associated with acute or potential tissue damage or described in terms of such damage.

It is a duality as it includes both a physiological and psychological aspects.

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2
Q

What is the definition of nociception ?

A

The neural physiological process of encoding and processing noxious stimuli.

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3
Q

What is congenital analgesia ?

A

it is a genetic disorder which involved people feeling no pain.

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4
Q

What is the name of the system that monitors the position of limbs in space ?

A

Proprioreception.

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5
Q

During genetic analysis, what gene was inactivated and what did this gene code for? Why did this result in people not being able to recognise pain ?

A

SCN9A is the gene which codes for voltage-gated sodium channel Nav 1.7.

Nav1.7 is a target for pain. Inactivation of this gene would lead to loss of pain perception.

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6
Q

What type of mutation occurred in the SCN9A gene ?

A

Point mutation.

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7
Q

How many domains are there in voltage gated Na+ channels ?

A

4 domains.

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8
Q

Which transmembrane (S1-S6) domains sense small depolarisations/ sense voltage ?

A

S1-S4

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9
Q

Which transmembrane (S1-S6) domains make up the pore of the voltage gated Na+ channels?

A

S5-S6

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10
Q

What happened when Nav1.7 was removed from a mouse. What happened when Nav1.7 was added to a mouse?

A

Removal, no pain perception.

Addition, spontaneous pain which was unprovoked.

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11
Q

True/ false: Making an inhibitor of the Nav1.7 would therefore be a strategy to make an analgesic drug ?

A

True

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12
Q

What is the basic nociceptive pathway?

A
  1. Nociceptor neurone: Picks up harmful stimuli such as injury, pressure, temperature and pH.
  2. Projection neurone: leads to the brain
  3. Tertiary neurone: located in the brain
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13
Q

What is the pathway for the nociceptor?

A 
Target tissue
Peripheral nerve 
Dorsal root ganglion 
Dorsal root 
Spinal cord
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14
Q

True or false: The nociceptor is a pseudounipolar neurone with a peripheral and central axon

A

True

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15
Q

What stimuli do nociceptors detect?

A

Specialised to detect high threshold noxious stimuli

Heat and cold 
High threshold mechanical stimuli 
Certain chemicals (capsaicin)
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16
Q

What channels can detect these stimuli ?

A

Specific cation channels

17
Q

What is the receptor for capsaicin?

A

TRPV1, which detects noxious heat

18
Q

How many transmembrane ion channels and subunits does TRPV1 have?

A

6 transmembrane ion channels

4 subunits form

19
Q

What ions are permeable to TRPV1?

A

Na+ and Ca2+

20
Q

How can depolarisation occur from TRPV1?

A

In response to eating, the channel opens which leads to ion influx. This depolarises the membrane

21
Q

What are the tetrodotoxin sensitive sodium channels ?

A

Nav1.1
Nav1.6
Nav1.7

22
Q

What are the tetrodotoxin insensitive sodium channels?

A

Nav1.8

Nav1.9

23
Q

What fibres are involved in nociception and what are their features?

A

A(gamma) fibre

  • Lightly mylinated
  • Medium diameter

C fibre

  • Unmyelinated
  • Small diameter
24
Q

What fibre is involved in proprioception and light touch?

A

A (beta) fibre

  • Myelinated
  • Large diameter
25
Q

What is the main transmitter in nociceptors?

A

Glutamate

substance p

26
Q

What facilitates the transmitter release ?

A

Voltage gated calcium channels Cav2.2

27
Q

What receptor detects glutamate at the post synaptic neurone ?

A

AMPA receptors aka glutamate receptors

This is a ligand gated ion channel as it is activated once glutamate binds

28
Q

Besides AMPA receptors, what other glutamate receptors are there ?

A
  • NMDA receptors
  • Kainate receptor
  • Metabotropic receptor
29
Q

What receptor does glutamate predominantly bind to ?

A

AMPA

30
Q

What channels are glutamate released by ?

A

Ca2+ channels

31
Q

What inhibitory neurones are involved in the nociceptor

A

GABA

32
Q

What region on the brain, when stimulated can cause intense analgesia ?

A

PAG

33
Q

What region of the brain releases inhibitory transmitters ?

A

Opioid peptides
5HT
NA

34
Q

How do acute MOP receptor function?

A
  • Inhibition of adenylyl cyclase and reduction in cAMP
  • Increases opening K+ channels and hyperpolarization
    (membrane cannot depolarise easily)
  • Decrease opening ca2+ channels
  • Reduced neuronal excitability

Pain (20 decks)

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