Ion Channels in Pain Pathways - capsaicin and other ion channel targets

Question 1

What is capsaicin?

Answer 1

Active ingredient in chillis
Activates TRPV1 receptor on the nociceptor neuron
Is eventualy neurotoxic to cells expressing TRPV1, ‘defunctionalising’ them
Initial application to the skin causes a burning sensation (may use a EMLA cream alongside)

Question 2

Why can capsaicin not cure the disease / the pain will come back?

Answer 2

Eventually the desensitised nerve will grow back

Analgesia generally for symptomatic relief

Question 3

How is it used in an analgesic cream if it is painful itself?
Calcium effect

Answer 3

Continuous stimulation of the TRPV1 receptors has a persistant effect.
The receptor opening allows significant flow of Ca2+ into nerve fibres
Ca2+ can also be released from endoplasmic reticulum because TRPV1 is expressed on intracellular organelles too
Sustained high levels of intracellular calcium can activate calcium-dependent enzymes such as proteases and can introduce the depolymerisation of cytoskeletal components such as microtubules
Capsaicin can inhibit mitochondria by binding; it then competes with ubiquinone to inhibit the electron transport chain which reduces the transmembrane potential from mitochondria –> USELESS

Question 4

How does black mamba venom kill?

Answer 4

Inhibits voltage-gated potassium channels

Binds to muscarinic receptors

Question 5

How were peptides extracted from the mamba venom turned into a novel drug?

Answer 5

Two peptides shows to inhibit ASIC1a channels
Mambalgin-1 and 2 inhibits acute and inflammatory pain
Not sensitive to naloxone
Dpoendent on the presence of ASIC1a