Opioids operate as pro-inflammatory cytokines, resulting in neuroinflammation in the CNS

[pattismith]

(PDF) Toll-Like Receptor 4 (TLR4)/Opioid Receptor Pathway Crosstalk and Impact on Opioid Analgesia, Immune Function, and Gastrointestinal Motility (researchgate.net)

review 2020

 

[pattismith]

To explain morphine-induced persistent sensitization, a positive feedback loop has been proposed; this involves an initial morphine-induced amplified release of IL-1β and a subsequent exacerbated release of DAMPs, which increases the activation of TLR4 and the purinergic receptor P2X7R.

 

[ljimbo423]

I took morphine many years ago for severe fibromyalgia pain. Very soon after I started a very low dose, my ME/CFS got much, much worse. This could very well explain why.

 

[pattismith]

I took morphine many years ago for severe fibromyalgia pain. Very soon after I started a very low dose, my ME/CFS got much, much worse. This could very well explain why.

I took two years Tramadol for neuropathic pain and got two years of major depression when I stopped.

Every time I take opioids on a regular basis, I feel very good the first day, and I feel like shit every days after...

 

[ljimbo423]

Every time I take opioids on a regular basis, I feel very good the first day, and I feel like shit every days after...

Looking back on my last BIG relapse that took me from mild to severe, I think morphine played a big part in that. I'll never take it again!

 

[bensmith]

I wonder if kratom should be explored or if it’s the same outcome

 

[helen1]

@bensmith
I’ve explored it: same outcome for me. Some people can use it for a longer time before the consequences happen.

 

[belize44]

This is a disturbing concept.

 

[Violeta]

Would this include gluten?

Cereals activate TLR4

https://www.nature.com/articles/ni.2530

 

[Violeta]

Involvement of corticotropin-releasing hormone receptor subtypes 1 and 2 in peripheral opioid-mediated inhibition of inflammatory pain​

https://www.sciencedirect.com/science/article/abs/pii/S0304395903003026

In painful inflammation, exogenous as well as endogenous corticotropin-releasing hormone (CRH) can release opioid peptides (mainly β-endorphin) from various types of immune cells and produce antinociception by activating opioid receptors on peripheral sensory nerve endings. CRH mediates its central effects through two high-affinity membrane receptors, the CRH receptor subtypes 1 and 2. It is unclear at present whether the peripheral antinociceptive effects of CRH are mediated through CRH receptor 1 (CRH R1) or CRH receptor 2 (CRH R2).

From Pattismith's study:

Opioids operate as pro-inflammatory cytokines, resulting in neuroinflammation in the CNS, but they mediate immunosuppressive effects in the peripheral immune system. It is apparent that TLR4/opioid receptor pathway crosstalk varies dependent on the cell type and activating stimulus.


Anyone have thoughts on how this relates to Dr Vernon's information about CRFR1 and 2?

She talks about it in this article.
https://forums.phoenixrising.me/thr...-crack-the-case-of-me-cfs.89200/#post-2432075

 

[datadragon]

This seems to tie in also with orexin receptors:

Sleepiness and decrease in attention are dose-limiting side effects of opioids. The orexin/hypocretin system plays an important role in maintaining wakefulness. This study aimed to explore the potential of a nonpeptide orexin receptor agonist to alleviate morphine-induced sedative effects. Effects of intracerebroventricular orexin-A and systemic orexin type-2 receptor agonist, YNT-185, on EEG changes induced by morphine were examined. Orexin-A and/or YNT-185 attenuated morphine-induced sedative effects assessed by EEG changes and behavioral measures in rats. The authors' results suggest that orexin-2 receptor activation alleviates morphine-induced sedative effects. https://pubmed.ncbi.nlm.nih.gov/29521652/