Is ME/CFS pain caused by coxsackievirus B activating TRPV1, a receptor involved in pain, inflammation and regulating body temperature?

[Hip]

Coxsackievirus B activates the TRPV1 receptor in order to induce mitochondrial fission. Ref: here

Mitochondrial fission is where mitochondria divide into two smaller mitochondria. For the benefit of their own survival, some viruses, including CVB, induce mitochondrial fission to support infection, and to disrupt antiviral immunity.

The TRPV1 receptor (transient receptor potential vanilloid 1) plays a major role in pain, inflammation and body temperature regulation. TRPV1 is activated by capsaicin (from chilli peppers). Ref: here

So I wonder if coxsackievirus B-activated TRPV1 might explain the muscle or joint pain felt by some ME/CFS patients?

In IBS, increased TRPV1 nerve fibres are observed, and it is thought these might contribute to the pain felt in IBS. Ref: here

If activated TRPV1 is involved in ME/CFS pain, then TRPV1 antagonists might alleviate this pain. This paper says:

TRPV1 antagonists are effective in treatment of chronic intractable pain secondary to cancer, migraine, AIDS or diabetes, urinary urge incontinence, chronic cough, and irritable bowel syndrome.

According to an article, there has been intense research to develop TRPV1 antagonists, and there are many orally active TRPV1 antagonists in clinical development, including:

TRPV1 Antagonists

• Capsazepine — blocks the sensation of heat caused by capsaicin. Wikipedia
• A-425619
• SB-705498 — tested as a chronic cough treatment. Wikipedia
• SB-366791 — used in research into pain and inflammation. Wikipedia
• SB-452533
• SB-782443 — a nicotinamide derivative
• ABT-102
• AMG-517 — treatment for chronic pain. Wikipedia
• AMG-9810 — has analgesic and antiinflammatory effects. Wikipedia
• AMG-0347 — tested in a postoperative pain clinical trial

Unfortunately these TRPV1 antagonists are still in the research pipeline.

One TRPV1 inhibitor which is available is menthol, which is found at 40% in peppermint oil. Menthol activates TRPM8, which in turn inhibits TRPV1. This may explain why peppermint oil is effective for IBS pain.



TRPV1 antagonists used in ME/CFS may not only treat pain, but inhibiting TRPV1 has antiviral effects against coxsackievirus B; this study says:

Our preliminary findings suggest that CVB relies on TRPV1-mediated mitochondrial fragmentation, and treating cells with the specific TRPV1 inhibitor, SB-366791, potently reduces CVB infection.

TRPV1 antagonists may also fight COVID infection, according to this paper.

 

[katabasis]

That first reference is really interesting to me. I wonder though, whether antagonism of TRPV1 might cause it to eventually upregulate. Since a lot of the viral infections associated with CFS are difficult to eradicate, even with prolonged treatment, I wonder whether menthol would really be effective when you're looking at a prolonged course in whole human body. Maybe something like honokiol, a compound found in magnolia bark, might be effective, since it appears to downregulate TRPV1. Though with that, there is also the issue that honokiol is a PAM of GABA receptors, so it might be habit forming with prolonged use.

 

[Hip]

I wonder though, whether antagonism of TRPV1 might cause it to eventually upregulate.

I don't know, but I guess it is possible, as I read that the reverse is true: if you strongly agonise TRPV1 (using capsaicin for example) this receptor will start to down-regulate in its sensitivity.

I wonder whether menthol would really be effective when you're looking at a prolonged course in whole human body.

I don't think menthol is a going to be a great antiviral for coxsackievirus B, unfortunately.

In a mouse study, the antiviral effects of menthol on coxsackievirus B (arising from its antagonism of TRPV1) only resulted in a 69% reduction in pancreas coxsackievirus B levels, when given at an oral dose of 100 mg/kg daily to the mice.

The mouse 100 mg/kg dose of menthol equates to a 650 mg oral dose for an 80 kg human.

I actually take 250 mg of menthol dissolved in oil as a treatment for my IBS sometimes.


However, if we could get hold of some of the TRPV1 antagonists in the research pipeline which are mentioned in my above post, then the antiviral effects may be stronger.

 

[Pendergast]

This is really interesting... The only thing that worked with my chronic nausea (one of my most debilitating symptom), in it's worst, was capsaicine....

Also, the thing that worsen my nausea the most is cannabis, which I think interacts with the TRPV1 too.

And I have positive IgGs to Coxsackie B too.....

@Hip , nice info as always.... Sorry to read in another post that you are worse cognitively from Covid... Your posts are awesome. Hoping you gettint better soon.

A big hug!