Pain 3 Flashcards
Where is Nav1.7 expressed
Expressed principally in sensory and sympathetic ganglia. Smaller/ medium cells involved in nociception. Very low expression in the CNS
What tool was used to study Nav1.7 KO
Didn’t want to do global gene deletion as expression is not hugely restricted. So tissue specific deletion via Cre/LoxP deletion
Where was Cre expression forced
Small and medium DRG neurons ONLY
What was the result of an Nav1.7 deletion in Nav1.8 positive neurons
Mice had resistance to mechanical noxious pressure
Inflammatory pain had also been abolished
How was the effect of Nav1.7 deletion in 1.8 positive neurons
Look at sensitivity of cells before and after injection of inflammatory agent. After deletion - threshold in mechanical and thermal pain remained unchanged before and after injection
What was the effect of causing death in 1.8 positive DRG neurons
resistant to cold pain and acute pressure, also inflammatory pain, no change in neuropathic pain
How did they delete all DRG neurons in the floxed mouse
Advillin-Cre transgenic mouse - Active in DRG but not SCG
How did they delete all PNS neurons in the floxed mouse
Wnt1-Cre is active in SCG and DRG - all of the PNS
Which mouse model was capable of attenuating neuropathic pain
Deletion of Nav1.7 in ALL DRG and sympathetic neurons
What is the result of a gain of function mutation in Nav1.7
Primary erythermalgia as well as familial rectal pain
What is the result of loss of Nav1.7 in mice and humans
Increases endogenous opioid precursor expression
Nav1.7 loss of function in humans?
Complete loss of pain
