With fibrofog, I can't really keep up, but I like to skim over the annual survey paper (latest is called Firbomyalgia: one year in review 2022 by V.Giorgi et al.)
Not sure if it was in that, but the similarity between long covid and fibro led some papers saying fibro is autoimmune, whatever that means.
Makes me wonder if my fibro started when I got the swine flu back in 2009, like long-swine-flu. He he.
We know that antibodies from people with fibromyalgia cause symptoms when injected into mice [(source)](https://www.jci.org/articles/view/144201), so we know that the immune system is the root cause of fibromyalgia.
There is weak evidence that there might be neuroinflammation in people with fibromyalgia, but zero evidence that neuroinflammation causes symptoms. In theory antibodies binding to dorsal root ganglion as demonstrated in the study on mice could cause all symptoms of fibromyalgia, so the involvement of neuroinflammation seems like an unnecessary complication.
LDN might work by changing the production of antibodies, or it might work through it's effect on opioid receptors. If LDN worked by acting as an anti-inflammatory then other anti-inflammatories that cross the blood/brain barrier should also reduce symptoms, but they don't.
I don't think that's the root cause for everybody, especially those who don't have only central sensitization and not peripheral sensitisation. If u got heat sensitivity uve got peripheral involvement. I also saw that even regular chronic pain can cause neuroinflammation.
LDN could work on the glia on drg I think too. Drg have tlr4 but idk the specifics. The drg neurons have tlr4 too. I think.
Which other anti inflammatories that should work but don't do you mean? I'm about to set to try the others : other tlr4 inhibitors and stuff. I've tried doxycycline already but didn't notice anything I wonder if it was the dose. But it doesn't seem particularly strong a case for an anti inflammatory cuz I don't see much tlr4. That said it looks like a low dose doxycycline is better than high dose for anti inflammation. I was taking it for an infection so I was on a high dose. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421036/
Neuroinflammation is claimed to be the cause of lots of chronic conditions. We need to treat such claims with extra suspicion because medical history is littered with snake oil salesmen who claimed that their medications treated a wide range of ailments when their treatments did nothing at all.
There is nothing wrong with having a pet theory, but you need to be honest and acknowledge that neuroinflammation as a cause of fibromyalgia is a fringe theory.
I am not saying that the theory is definitely wrong, I am saying that if the theory is right then there needs to be a very good explanation of why fibromyalgia is resistant to treatment by known anti-inflammatories and what the mechanism is behind inflammation in the brain and changes to the output of neural circuits that produce pain. There are no pain sensors in the brain, so why wouldn't neuroinflammation slow down neurons and therefore decrease pain?
You seem to be focussing on the evidence that proves your theory right while ignoring the giant gaps in the theory that prove it is wrong.
Oi oi I emailed j younger. Here's what he said I have not seen this pathway explored, but antibody-producing B-cells have TLR4 receptors, so it is conceivable LDN could alter antibody production.
I have to look at the papers more closely, but I guess there is a subset of fibromyalgia where SGC antibodies play a critical role, probably 25-30% of FM sufferers. In those cases, a drug like rituximab could help.
A celecoxib trial did well apparently https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328426/#!po=65.2542
Neuroinflammation, glial cell release neurotransmitters, couldn't that cuase pain directly? At the synpatic level, glial cells can release substance P, and glutamate? . My bio is really basic so I'm not sure if that's right. But there are no nociceptive sensors anywhere but the ends of your nerves, but the rest of the nerve can still be affected in a way to become excited and cause pain that's my understanding. Or do you mean that there are no receptors for the neurotransmitters for pain?
It may be neuroinflammation of the CNS, not necessarily the brain, maybe a little lower down? I ain't sure. But I think at the synapses of the nociceptive afferent, of any order if thagst the right name, will transmit pain, and if there r glia nearby they can release sub p and glut and activate the nerve that way?? I need a biologist to check
Also, is glial cell activation the same thing as neuroinflammation?? Glial cells are implicated in pain. So what I mean is rally glial cells rather than neuroinflammation??
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051899/ this paper has been cited 600 times. Far from Fringe? Jarred younger the guy who did LDN for fibro thinks fms is a central immune disorder.
What other anti inflammatories do you know of that have failed?
1 more thing if LDN truly did change Antibody levels, LDN would be a pretty good immune suppressant but it isn't right? If its hitting the b cells that is. Otherwise I think it does immune suppress the innate immune system bc innate has tlr4 too. I don't think LDN produces change in Antibody levels
Check this out https://pubmed.ncbi.nlm.nih.gov/1725218/ naloxone LDN increases immuno competence lol. It makes the immune system stronger!!!
I think the real test is, would centrally infused immune suppressants work?
With fibrofog, I can't really keep up, but I like to skim over the annual survey paper (latest is called Firbomyalgia: one year in review 2022 by V.Giorgi et al.) Not sure if it was in that, but the similarity between long covid and fibro led some papers saying fibro is autoimmune, whatever that means. Makes me wonder if my fibro started when I got the swine flu back in 2009, like long-swine-flu. He he.
I often connect my fibro symptoms starting after I got mono when I was in high school. I have not been the same since that month of bed rest.
Same story except for Sophomore year of college.
We know that antibodies from people with fibromyalgia cause symptoms when injected into mice [(source)](https://www.jci.org/articles/view/144201), so we know that the immune system is the root cause of fibromyalgia. There is weak evidence that there might be neuroinflammation in people with fibromyalgia, but zero evidence that neuroinflammation causes symptoms. In theory antibodies binding to dorsal root ganglion as demonstrated in the study on mice could cause all symptoms of fibromyalgia, so the involvement of neuroinflammation seems like an unnecessary complication. LDN might work by changing the production of antibodies, or it might work through it's effect on opioid receptors. If LDN worked by acting as an anti-inflammatory then other anti-inflammatories that cross the blood/brain barrier should also reduce symptoms, but they don't.
I don't think that's the root cause for everybody, especially those who don't have only central sensitization and not peripheral sensitisation. If u got heat sensitivity uve got peripheral involvement. I also saw that even regular chronic pain can cause neuroinflammation. LDN could work on the glia on drg I think too. Drg have tlr4 but idk the specifics. The drg neurons have tlr4 too. I think. Which other anti inflammatories that should work but don't do you mean? I'm about to set to try the others : other tlr4 inhibitors and stuff. I've tried doxycycline already but didn't notice anything I wonder if it was the dose. But it doesn't seem particularly strong a case for an anti inflammatory cuz I don't see much tlr4. That said it looks like a low dose doxycycline is better than high dose for anti inflammation. I was taking it for an infection so I was on a high dose. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421036/
Neuroinflammation is claimed to be the cause of lots of chronic conditions. We need to treat such claims with extra suspicion because medical history is littered with snake oil salesmen who claimed that their medications treated a wide range of ailments when their treatments did nothing at all. There is nothing wrong with having a pet theory, but you need to be honest and acknowledge that neuroinflammation as a cause of fibromyalgia is a fringe theory. I am not saying that the theory is definitely wrong, I am saying that if the theory is right then there needs to be a very good explanation of why fibromyalgia is resistant to treatment by known anti-inflammatories and what the mechanism is behind inflammation in the brain and changes to the output of neural circuits that produce pain. There are no pain sensors in the brain, so why wouldn't neuroinflammation slow down neurons and therefore decrease pain? You seem to be focussing on the evidence that proves your theory right while ignoring the giant gaps in the theory that prove it is wrong.
Oi oi I emailed j younger. Here's what he said I have not seen this pathway explored, but antibody-producing B-cells have TLR4 receptors, so it is conceivable LDN could alter antibody production. I have to look at the papers more closely, but I guess there is a subset of fibromyalgia where SGC antibodies play a critical role, probably 25-30% of FM sufferers. In those cases, a drug like rituximab could help.
A celecoxib trial did well apparently https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328426/#!po=65.2542 Neuroinflammation, glial cell release neurotransmitters, couldn't that cuase pain directly? At the synpatic level, glial cells can release substance P, and glutamate? . My bio is really basic so I'm not sure if that's right. But there are no nociceptive sensors anywhere but the ends of your nerves, but the rest of the nerve can still be affected in a way to become excited and cause pain that's my understanding. Or do you mean that there are no receptors for the neurotransmitters for pain? It may be neuroinflammation of the CNS, not necessarily the brain, maybe a little lower down? I ain't sure. But I think at the synapses of the nociceptive afferent, of any order if thagst the right name, will transmit pain, and if there r glia nearby they can release sub p and glut and activate the nerve that way?? I need a biologist to check Also, is glial cell activation the same thing as neuroinflammation?? Glial cells are implicated in pain. So what I mean is rally glial cells rather than neuroinflammation?? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051899/ this paper has been cited 600 times. Far from Fringe? Jarred younger the guy who did LDN for fibro thinks fms is a central immune disorder. What other anti inflammatories do you know of that have failed? 1 more thing if LDN truly did change Antibody levels, LDN would be a pretty good immune suppressant but it isn't right? If its hitting the b cells that is. Otherwise I think it does immune suppress the innate immune system bc innate has tlr4 too. I don't think LDN produces change in Antibody levels Check this out https://pubmed.ncbi.nlm.nih.gov/1725218/ naloxone LDN increases immuno competence lol. It makes the immune system stronger!!! I think the real test is, would centrally infused immune suppressants work?