I have re-read through the thread. There were several ideas I chucked in and I think their strengths and weaknesses have been explored fairly well. The main idea was just to think of bone marrow as a place we have forgotten. TLR7 was suggested as a candidate signal that might provide an example of how ME/CFS might have some similar parameters to lupus. I think it does have some specific connections of interest but I wouldn't want to limit thoughts to it at all. There are a few points I think may be worth adding.
1. The sensitivity of bone marrow to pressure shows it has good innervation - maybe more obviously so than lymph node but that may be spurious. So it could talk directly to brain. Cellular changes might send signals to brain via cytokine sensitive nerves and brain might modulate cell behaviour through ACh or neuropeptide transmitters.
I have to say that I don't terribly like this idea, it is just that without any circulating cytokines to blame we are a bit stuck for why the brain gets tampered with. I think immune system loops, where a cell of a type encourages, directly or indirectly, other members of the same cell type to do the same bad things it is doing are plausible (and documented in other situations). I think brain loops where certain neurons encourage other neurons to encourage them to encourage other neurons.. are plausible. A loop where immune cells of a type signal to the brain which then signals back to other cells of that type to do more bad things is conceivable but I see pretty little evidence from other diseases, despite it being a trendy sort of story for brain to collude with body tissues.
I rather doubt that any of this would be reflected in bone pain to be honest, although it is possible.
2. I am not sure we have a good idea what cytokines will do in bone marrow. I don't. There may be literature though. Two things are unusual. Firstly, red marrow space is a fairly rigid box so the vasodilatation of inflammation may not apply much. In inflammation small vessels get wider and more blood goes through but often slower, to allow cell migration. I don't see that as a likely option for marrow where blood vessel dilatation is likely to speed up flow (no room for dawdling).
Also the marrow is already full of 'inflammatory' cells like neutrophils and monocytes. Moreover, there is no tight endothelial barrier so cell emigration is not going to require the usual upregulation of adhesion molecules. Spleen is rather similar. And because bone marrow has a rigid case it cannot take up extra immigrant cells as easily as other tissues anyway.
I am not aware of a disease where there is sterile inflammation of bone marrow and maybe there isn't such a thing, for these reasons. In oseteomyelitis there is pus and necrosis and red marrow is replaced by granuloma-type organisation with dying polymorphs and palisades of walling off macrophages and fibroblasts. But without cell death and pus I am not sure what "bone marrow inflammation" would look like.
3. People have mentioned red cells and haemophagocytosis, which is engulfment of whole red cells. I doubt that is relevant but another point is that the bone marrow is the place where nucleic acids from developing red cells, chucking it all out as they become haemoglobin balloons, are taken up and processed in vast quantities all the time. The same will apply to nucleic acids from pre-B cells that get deleted in marrow after failing to develop a safe (not autoimmune) surface antibody species. In lupus nucleic acid is recognised in an inappropriate way by antibody and that leads to cycles of immune complex formation, local neutrophil influx, further cell death with release of more nucleic acid etc. In health all the nucleic acid is tidied away silently.
