Thank you to Ellfindoe for being patient and explaining so well. I hope you don’t mind, but I have taken what you have said and put it in my own words to try to ensure that I understand what you have said. Here goes …..
The latest model of RLS is that there is a series of factors which lead to RLS. What seems to be the main differences between people with RLS and those who don't have it can be –
1. People with RLS have a failure in transporting iron from the blood into the brain across what is known as the Blood Brain Barrier (BBB). This can lead to a condition called Brain Iron Deficiency. BID in turn, causes a reduction in the activity of a neurotransmitter called "adenosine", which leads to two problems: (a) excessive levels of dopamine, a neurotransmitter and (b) excessive levels of glutamate, another transmitter. Excess glutamate can lead to "hyperarousal" and Periodic Limb Movement Disorder and, and excess dopamine can lead to “sensory-motor symptoms” and Periodic Limb Movement Disorder.
2. People with RLS have less Dopamine Receptors (otherwise known as D2, which are protein receptor sites which mediate the cognitive flexibility in humans) in their Dopaminergic Neurons. Dopaminergic Neurons, found in the midbrain, are the main source of dopamine in the central nervous system and their loss is associated with one of the most prominent human neurological disorders, Parkinson's disease. (Note from Lotte just received : “DAs seem to target the D3 receptors, thus not (so much) the D2 ones that are reduced in people with RLS.”)
* So in Case No 1, Brain Iron Deficiency leads to excessive levels of two transmitters, Dopamine (which enables neurons in your brain to communicate and control movement )and Glutamate (a brain chemical that either excites or inhibits the function of neurons), both of which cause RLS.
* And in Case 2, lack of Dopamine Receptors leads to the brain being unable to “process” the Dopamine (ie insufficient dopamine biosynthesis in the dopaminergic neurons) that is produced by the Dopaminergic Neurons, which also causes RLS.
Dopamine Receptor Agonists directly stimulate the Dopamine Receptors, and Gabapentinoids, Gabapentin and Pregabalin work by reducing Glutamate levels, i.e. the other aspect of RLS. Because these reduce "nerve sensitivity" they have a general calming effect on RLS, nerve pain and epilepsy.
So by taking Gabapentin, one is not “replacing” the Ropinirole, because the Ropinirole is a Dopamine Agonist, and the Gabapentin is targeting the Glutamate. By coming off Ropinirole, your Dopamine Receptors are back to square one again – ie not so many of them, not producing and not processing the dopamine in your brain. However, what you are doing by taking the Gabapentin is to concentrate on the over production of Glutamate caused by the failure in transporting iron from the blood into the brain the Blood Brain Barrier, which in turn leads to nerve sensitivity.
QUESTIONS PLEASE
If I have understood all this correctly, my first question now is “has it been proved beyond reasonable doubt that all RLS suffers do have Brain Iron Deficiency? Because if not, then those that do not have it, will not have excessive amounts of Glutamate”. My second question is “if there are no excessive amounts of Glutamate, what effect will taking Gabapentin have on the normal amounts of Glutamate found in a normal body”.
Please feel free to correct any of the above. I will be a lot happier when I get a true over view of my problem! Big thanks to all, Sally
And to complete the picture ... direct from Ellfindoe “Another approach to RLS is to correct the BID using iron therapy. A more recent development is the experimental use of dipyridamole, which increases adenosine.”
Some Answers
Dr Berkowski Article on Dopamine Agonists Oct '23.
RLS and Glutamate?
The link between Iron and RLS
