Ion Channels in Pain Pathways - Sodium Channels Flashcards
What does a mutation in gene SCN9A on chromosome 2q24 cause? What does this mean in terms of pain pathway?
The mutation means that SCN9A gene is inactive and this means that the protein it codes for cannot be synthesised. In this case it is the votage-gated sodium channel Nav1.7 that is a target in pain
What kind of mutations can occur affecting Nav1.7? What effect does this have on the person?
Loss of function where the protein is not coded for - no pain / human pin cushion
Gain in function, the patient may experience spontaneous pain
Where are Nav1.7 channels found?
Schwann cells and PNS
Where are Nav1.8 and 1.9 channels found?
DRG
Where are Nav1.5 channels found?
Heart
Where are Nav1.1 *PNS, 1.2 and 1.3 channels found?
CNS
Explain the steps causing an action potential at the peripheral terminal
Noxious stimuli induced ligands to stimulate the ligand gated channels on the terminal e.g ATP at P2X3, H+ at ASICs and capsaicin at TRPV1 etc
This summative effect leads to a generator potential opening voltage gated channels at the peripheral terminal e.g. Nav1.7, 1.8 and 1.9 etc.
This contributes to the generator potential further until it reaches the threshold needed to fire off an action potential along the axon to the DRG
When can Nav1.7 be upregulalted?
In inflammation
Where is Nav1.7 expressed and what is its role?
Expressed in the DRG and sympathetic ganglion neurons
Amplifies the generator potentials in neurons it’s present on, including nociceptors
It is a threshold channel for firing action potentials
Where is Nav1.8 expressed and what is its role?
A sensory neuron specific channels, preferentially expressed in the DRG and trigeminal ganglia (head)
Contributes most of the sodium current underlying the action potential upstrokes in neurons that express it
Which three ways can sodium channel blockers be categorised?
- based on selectivity for individual sodium channel isotopes
- based on the state of the channel they target
- based on a combination of the two
What kind of sodium channel blockers can be used as analgesic?
Non-specifics e.g. carbamazapine, phenytoin, lidocaine
What is carbamazapine? How does it work?
Anti-convulsant
Stabilises the inactivated state of the channel
What is phenytoin? How does it work?
Anti-convulsant
Stabilises the inactivated state
Second choice for trigeminal neuralgia after carbamazapine
What is lidocaine? How does it work?
Local anaesthetic
Inhibits open/inactivated channel
