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BMSC - Anaesthetics and Analgesia > Pain and TRPV1 > Flashcards

Pain and TRPV1 Flashcards

1
Q

What is TRPV1?

A

The capsaicin receptor

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2
Q

What is odd about the TRPV1 channel?

A

It conducts Na, K, Ca and Mg

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3
Q

Which ions influx through TRPV1 on capsaicin binding?

A

Na+

Ca2+

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4
Q

TRPV1 channels and more permeable to Ca2+ , but they conduct more Na+ - why?

A

Purely bc theres more Na+ outside the cell then Ca2+

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5
Q

Outline the events upon acute activation of the TRPV1 channel

A

Membrane depol and excitation
Release of proinflam peptides (CRGP, sub P)
Perceived sensation of warming, itching, stinging and burning
Increased sensitivity

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6
Q

Does substance P act centrally or peripherally?

A

Peripherally

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7
Q

What occurs with chronic activation of TRPV1?

A

Desensitisation and defunctionalisation

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8
Q

Outline desensitisation and defunctionalisation of TRPV1 channels

A

Repated Ca2+ influx
Excitotoxic damage
Disruption of cytoskeleton of the cell and breakdown of FAT

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9
Q

Outline the structure of the TRPV1 channel

A 
838 amino acid protein with a molecular mass of 95kDA
Intracellular N and C termini
6 transmembrane domains 
P loop sequence
Forms a tetramer
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10
Q

Many TRPV1 agonists contain the amide chain…

A

Vanillyl

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11
Q

Give examples of botanical agonists of TRPV1

A

Piperine (peppercorn)
Gingerol (ginger)
Zingerone
Camphor (menthol)

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12
Q

Which endogenous compounds agonist TRPV1?

A

Endovillanoids

anadmide, arachidonic acid

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13
Q

Which agonist is essentially irreversible of TRPV1?

A

Double knot toxin from the Chinese bird spider

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14
Q

What activates TRPV1 channels?

A

Noxious heat >43C
Acidosis
Intense membrane depols

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15
Q

Acidic environments make TRPV1 most sensitive to capsaicin

T/F

A

T

Tominga et al 1998

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16
Q

The capsaicin response curve shifts to the …… in acidic pH

A

Left

17
Q

What may make TRPV1 channels sensitive to non-noxious temperatures

A

Significant drop in pH

Unlikely to occur systemically - probs more local like MI

18
Q

Stimulus which activates TRPV1 channels much come from an intense. single stimulus
T/F

A

F

Different stimuli act synergistically on the channel to produce activation

19
Q

How are TRPV1 channels modulated?

A

Kinase dependent phosphorylation of target proteins

Done via the transfer of terminal phosphate of ATP to specific amino acids

20
Q

Which compounds are involved in functional modification?

A

Protein kinase C
Protein kinase A
CaMKII

21
Q

What is topical capsaicin used for?

A

Mild-moderate pain relief which accumulates when used several times a day over weeks

22
Q

Why are high concentrations of capsaicin put in cream for mod-severe pain?

A

Volatile and irritates gastric mucosa

23
Q

How are high volumes of capsaicin delivered?

A

Transdermal patch (with LA bc of the intense burning sensation)

24
Q

Transdermal capsaicin patches should be used daily to accumulate pain relief
T/F

A

F

Should be used as a once only treatment under supervision

25
Q

What is resiniferatoxin?

A

TRPV1 agonist used to treat overactive bladder

And cancer pain

26
Q

How is resiniferatoxin administered?

A

Intra-vesicular

27
Q

How does resiniferatoxin work?

A

Binds to TRPV1 and 4 expressing cells on the urothelium lining and sensory nerve fibres below the urothelium
Defunctionalise to make you need to pee less

28
Q

TRPV1 probably contribute to the transduction of acidic stimuli
T/F

A

T

Under certain circumstances

29
Q

How do we know that TRPV1 channels are active in >48C?

A

TRPV1 KO mice show normal response in tail immersion test up to 48C
Then increased latency

Increased latency to paw withdrawal at hot plate test but normal at lower temp

30
Q

Which three TRP channels are responsible for detection of noxious heat?

A

TRPA1
TRPM3
TRPV1

31
Q

Are all three TRP channels needed to sense noxious heat?

A

No, on KO of one the pain is still processed
Need to KO all three before there is no response to acute thermal stimulation

Caterina et al 2000

BMSC - Anaesthetics and Analgesia (8 decks)

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