Pain 2 Flashcards
What is tetrodotoxin
Potent blocker of alpha subunit. Binds the P-loop of channel pore on extracellular side.
What is the difference between TTX sensitive and insensitive channels
Sensitive have a binding affinity of 5-15nM whereas resistant channels need more than 1 micromolar conc of TTX is present.
Which Nav channels are resistant to TTX
Nav1.5, Nav1.8, Nav1.9
Why was it not possible to do in vivo drug studies with a specific blocker to a particular Nav channel
Nav channels are so similar in structure that there is no specific blocker capable of distinguishing one single channel from another
Which three models of pain behaviour were constructed in mice
1) acute pain thresholds to thermal and mechanical stimuli
2) Inflammatory pain models: examine the drop in acute thresholds following inflammation
3) neuropathic pain models: examine the drop in acute thresholds following damage to sensory nerves
How do you measure thermal thresholds in mice
Hargreaves device - mice go on a glass platford - lantern focuses light on a certain spot and records the time it takes the animal to feel uncomfortable and bring their paws up.
How do you measure mechanical thresholds
Von Frey hairs - plastic furs of differing thickness which dent at different forces. Apply these one by one and see which thickness causes discomfort to the animal
Where is Nav1.3 expressed
CNS and PNS - embryonic expression that fades away postnatally - lowest form of expression in the Nav family of channels
Which Nav channel is upregulated in chronic pain models
Nav1.3
What is the effect of Nav1.3 KO in mice
No effect on acute thermal, touch, pressure, inflammatory, neuropathic pain relief.
What is the contribution of Nav1.8 to pain
Nav1.8 expression wasn’t found in all cells of the DRG - expressed in medium and small cells only, which are required for noxious stimuli
What is the effect of Nav1.8 KO in mice
No effect on thermal, touch, neuropathic pain - Inflammatory pain was attenuated
What is the result of knocking down Nav1.8 in adult mice - by oligonucleotides
Analgesic results
What is the blocker for Nav1.8
muO-conotoxin MrVIB blocks Nav1.8 sensory neuron specific channels and chronic pain behaviour without motor deficits
What is A-803467.0
A potent and selective Nav1.8 sodium channel blocker
