Ion Channels in Pain Pathways; Capsaicin/ASICs Flashcards

1
Q

What is capsaicin?

A

The active ingredient of hot chili peppers; activates TRPV1 receptors localised on the nociceptor.

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2
Q

How is capsaicin cream used in analgesia?

A
  • Capsaicin eventually becomes neurotoxic to cells expressing TRPV1 (nociceptors); the nerve terminal degenerates, and TRPV1 is ‘defunctionalised’.
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3
Q

What capsaicin preparation are available?

A
  • Axsain cream; pain associated with posttherapeutic neuralgia (shingles) or diabetic neuropathy
  • Quentza; 8% capsaicin plaster used for neuropathic pain
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4
Q

How much capsaicin is required for analgesia?

A

A high concentration/low concentrations for continuous periods

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5
Q

How does capsaicin bring about enzymatic/cytoskeletal changes?

A
  • TRPV1 is Ca2+ gating
  • Activation allows significant amounts of Ca2+ to flow down its steep electrochemical gradient into nerve firbres
  • TRPV1 is also expressed in intracellular organelles; external capsaicin application causes release of Ca2+ from the ER
  • Results in sustained high levels of intracellular Ca2+
  • This ACTIVATES Ca2+ dependent enzymes such as proteases which induce the depolymerisation of cytoskeletal components e.g. microtubules (skeleton that holds nerve terminal together #getsrekt by its own enzyme)
  • Hence ‘defunctionalised’ terminal
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6
Q

How does capsaicin affect mitochondrial respiration?

A
  • At high capsaicin concentrations (much higher than required to activate TRPV1), capsaicin competes with UBIQUINONE to inhibit directly electron chain transport
  • Thus dissipating mitochondrial transmembrane potential and its respiring = impaired nociceptor function for extended periods
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7
Q

How does mitochondrial concentration increase at the peripheral terminal?

A

Can congregate there in response to NGF (nerve growth factor) but numerous present there OG.

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8
Q

Does capsaicin result in an irreversible loss of nerve fibres?

A

No; capsaicin exposure does not irreversibly overwhelm mitochondria function and nerve ending returns to health when capsaicin stimuli removed.

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9
Q

What does the venom (numerous toxins) of the black mamba do?

A
  • Inhibits voltage-gated potassium channels

- Binds muscarinic receptors

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10
Q

How do ASIC inhibitors relate to Mamba venom?

A
  • Two peptides (Mambalgin-1 and 2) from Mamba venom shown to inhibit ASIC1a channels
  • Inhibits ASIC currents in DRG neurones and CNS spinal neurones
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11
Q

How must mambalgin be give/what effect does it have?

A
  • Intrathecally (peptide)

- Inhibits acute (heat) and inflammatory pain

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