Unfortunately the abstract really doesn't do this paper justice. Had I been a reviewer, I would have asked them to rewrite it.https://www.sciencedirect.com/science/article/pii/S0166432819307703
There are several really interesting things discussed in the paper that I do not remember seeing elsewhere.
1) The authors studied mice that were triple genetic knockout for the mu, delta and kappa opioid receptors. They found that these mice were naturally low in serum iron at a level that is comparable to the iron starved mice that are usually used to study RLS. They concluded that the opioid receptors (possibly delta) play a role in determining iron levels throughout the body and in the brain.
2) The triple KO mice all displayed behaviors typical of RLS, including increased activity during the period when they should be resting with no reduction in activity during their active period.
3) They looked at thermal sensitivity of their tails and found that the triple KO mice had "thermal hypoaestheisia", namely, they showed a delayed reaction to thermal stimulation. That sounds a lot like something that we have discussed here in the past where some of us are able to handle hotter cookwear than non-RLS members of our families.
4) The triple KO mice also showed the same sort of disfunctions in their dopamine and glutamate systems as is found in RLS.
As a result, the authors may have opened the door to yet another part of the puzzle, namely the role of opioids and the possibility that RLS also includes some sort of disfunction in our natural opioid production (endorphins and met-enkephlins). It will therefore be very interesting to see what Dr Ferre comes up with in the study of the role of opioids that he is currently working on.