Review Potential pathophysiological role of the ion channel TRPM3 in ME/CFS and the therapeutic effect of low-dose naltrexone, 2024, Lohn et al

Full title:
Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone

Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with a broad overlap of symptomatology with Post-COVID Syndrome (PCS). Despite the severity of symptoms and various neurological, cardiovascular, microvascular, and skeletal muscular findings, no biomarkers have been identified. The Transient receptor potential melastatin 3 (TRPM3) channel, involved in pain transduction, thermosensation, transmitter and neuropeptide release, mechanoregulation, vasorelaxation, and immune defense, shows altered function in ME/CFS. Dysfunction of TRPM3 in natural killer (NK) cells, characterized by reduced calcium flux, has been observed in ME/CFS and PCS patients, suggesting a role in ineffective pathogen clearance and potential virus persistence and autoimmunity development. TRPM3 dysfunction in NK cells can be improved by naltrexone in vitro and ex vivo, which may explain the moderate clinical efficacy of low-dose naltrexone (LDN) treatment. We propose that TRPM3 dysfunction may have a broader involvement in ME/CFS pathophysiology, affecting other organs. This paper discusses TRPM3’s expression in various organs and its potential impact on ME/CFS symptoms, with a focus on small nerve fibers and the brain, where TRPM3 is involved in presynaptic GABA release.

https://translational-medicine.biom...s/Chronic Fatigue Syndrome (ME/CFS) is,2,3,4].

 

I suppose the only "potential" stems from Marshall-Gradisnik's publications which seemingly will never end up leading to anything useful?

 

LDN worked well for one of my ME symptoms for a couple of years, but had no effect on other symptoms. It seems to have different effects on other PWME. Maybe there's potential for a somewhat reliable treatment for one or more symptoms for some PWME, which is certainly of value for those people it does help. I certainly appreciate how it worked for me.

 

Could you say for what symptom you found it beneficial .

 

To determine if there's a genetic aspect I wonder if Decode ME follow ups could ask those who provided contact info for future research

if they had used LDN and
the nature of improvements/ effect

Or is this kind of thing not possible ?

 

Perceived muscle aches. There seemed to be no physical problem with the muscles. It felt like the aches common with getting the flu. At worst, they were full-body, but otherwise they were most severe in my front thigh muscles. LDN blocked those pain sensations completely. I didn't get the benefits that other people reported, such as reduction in lethargy or brainfog.

For me, LDN was a magical treatment. One morning I walked a few hundred meters, with unpleasant aches in my legs. I took a capsule of LDN. The next morning I repeated the walk, and when I reached the point I'd turned around, I felt fine, so I continued, climbed up a very steep hill, still felt ache-free, so continued several more km before deciding not to push it further. Great stuff! ... at least for me. I spent that winter doing multi-km hikes pretty much every day. After about 2 years of that, I found that I no longer had the aches, even without LDN.

 

Do you think it could have been immune activation and other problems in the muscles related to PEM, like what Wust et al. found.

 

I can't rule anything out, but the aches didn't correlate with muscle usage. Also, LDN was ~33% more effective when taken sublingually, which to me implies that it was working on the brain rather than the muscles.