I say this is about spasticity in the spinal cord injury and therefore it is relevent to spasticity in MS.
So understand how to control spasticity in spinal cord injury and you may know how to control spasticity in MS.
So in this study they find that in the motor nerves, which are the nerves between the spinal cord and the muscle, that you get alterations in sodium channel activity.
There are nine voltage dependent sodium channels (Nav) and Nav 1.6 is one of the important ones.
They are upregulated in demyelinated nerves and so is one of the targets for sodium channel blockers, which can be neuroprotective because they stop nerve energy depletion caused by the energy required to get rid of sodium from inside the cell.
In this study they find Sodium channels are increased in motor nerves, which may be part of the pathology or as a consequence of firing more often a occurs in spasticity. The sodium channels can be cleaved and deformation of the channel can lead to elevated calcium current and persistent sodium currents leading to spasticity. In this study they find that
calpain activation causes the cleavage of the sodium channel leading to spasticity. So this can be inhibited by calpain inhibitors and riluzole can block this sodium curent too...So this is the Nature Medicine....However some medicine I wonder.
This paper sort of makes my p**s boil........not because of the paper but it shows the luck of the draw when it comes to referees.
In this study the authors record spasms off a flexor muscle. What's the surprise in this?
Nothing as far as I'm concerned but when not a few months ago we where battling with editors from Nature Medicine and referees who say that spasticity is not a problem of flexor (bending muscles) and is just a problem of extensor muscles!
I say which bit of an extensor is causing these types of problem
Yep the frustration of publication.
Next up if riluzole is the exciting solution. What is the question?
In this study they use riluzole to inhibit spasms. This is a sodium channel blocker and glutamate receptor blocker.
Glutamate receptor stimulation increases calcium activation and so together they block influx of sodium and calcium which is going to stop depolarisation (loss of nerve membrane charge which occurs when a nerve fires. Sodium channels open allowing sodium to enter the cells causing the inside of the nerve to become more positively charged compared to the outside = depolarisation.