Ion Channels in Pain Pathways; Capsaicin/ASICs Flashcards
What is capsaicin?
The active ingredient of hot chili peppers; activates TRPV1 receptors localised on the nociceptor.
How is capsaicin cream used in analgesia?
- Capsaicin eventually becomes neurotoxic to cells expressing TRPV1 (nociceptors); the nerve terminal degenerates, and TRPV1 is ‘defunctionalised’.
What capsaicin preparation are available?
- Axsain cream; pain associated with posttherapeutic neuralgia (shingles) or diabetic neuropathy
- Quentza; 8% capsaicin plaster used for neuropathic pain
How much capsaicin is required for analgesia?
A high concentration/low concentrations for continuous periods
How does capsaicin bring about enzymatic/cytoskeletal changes?
- 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
How does capsaicin affect mitochondrial respiration?
- 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
How does mitochondrial concentration increase at the peripheral terminal?
Can congregate there in response to NGF (nerve growth factor) but numerous present there OG.
Does capsaicin result in an irreversible loss of nerve fibres?
No; capsaicin exposure does not irreversibly overwhelm mitochondria function and nerve ending returns to health when capsaicin stimuli removed.
What does the venom (numerous toxins) of the black mamba do?
- Inhibits voltage-gated potassium channels
- Binds muscarinic receptors
How do ASIC inhibitors relate to Mamba venom?
- Two peptides (Mambalgin-1 and 2) from Mamba venom shown to inhibit ASIC1a channels
- Inhibits ASIC currents in DRG neurones and CNS spinal neurones
How must mambalgin be give/what effect does it have?
- Intrathecally (peptide)
- Inhibits acute (heat) and inflammatory pain