Why RLS Patients Do Not Become Opioid Tolerant

[Oozz]

This question goes out to my fellow RLS experts. What would be your best guess as to why most RLS patients do not incur tolerance to opioids?

Based on my understanding, opioids act on the dopamine system via inhibition of gaba. This causes an in increase in dopamine production. There is also no receptor selectivity/preference with opioids. However, this process causes down-regulation of dopamine receptors and increase in dopamine transport in almost all human studies.

With that said, the lack of tolerance would only make sense if the reason opioids primarily work is not because of the dopamine increase.

[Rustsmith]

The opioids work by attaching to the opioid receptors. Most of the meds work via the mu-receptors and buprenorphine works via the kappa-receptors. This bypasses the blockage of the dopamine and glutamate receptors caused by the blocked adenosine receptors that are locked due to low iron.

As for why most RLS patients do not experience opioid tolerance similar to that experienced by chronic pain and those addicted, a likely reason is that the dose used to treat RLS is a small fraction of what they take. When most RLS patients on methadone take 5 to 10 mg/day and chronic pain patients take 40 to 120mg/day, it is no wonder that they start to build up a tolerance that is rare in RLS.