Hypothetical framework for post-COVID 19 condition based on a fibromyalgia pathogenetic model 2023,Martinez-Lavin et al

[Sly Saint]

Abstract


There is a clear clinical overlap between fibromyalgia, myalgic encephalomyelitis, and post-COVID 19 condition. Chronic fatigue, cognitive impairment, and widespread pain characterize these 3 syndromes. A steady line of investigation posits fibromyalgia as stress-evoked sympathetically maintained neuropathic pain syndrome and places dorsal root ganglia dysregulation with the ensuing small fiber neuropathy at the epicenter of fibromyalgia pathogenesis. This article discusses emerging evidence suggesting that similar mechanism may operate in post-COVID 19 condition.


https://link.springer.com/article/10.1007/s10067-023-06743-0

paywalled

 

[Ash]

What do they mean by “stress”, I wonder?
I find myself too stressed to look.

 

[rvallee]

What do they mean by “stress”, I wonder?
I find myself too stressed to look.

Judging from the references, looks to be cellular stress on nerve cells. They look quite good actually.

 

[Ash]

Judging from the references, looks to be cellular stress on nerve cells. They look quite good actually.

Oh great I was too afraid to look!

 

[SNT Gatchaman]

What do they mean by “stress”, I wonder?

Judging from the references, looks to be cellular stress on nerve cells. They look quite good actually.

Agree it seems fine. There is a nod to include psychology in there, but it's mostly about small fibre neuropathy and dorsal root ganglia.

ME/CFS is a complex illness typified by profound malaise after mental or physical effort occurring in patients already suffering from constant fatigue. The presence of musculoskeletal pain is implied in ME/CFS name.

There is an alternative explanation to the orthodox theory proposing fibromyalgia as a centralized “nociplastic” pain syndrome. This different model views fibromyalgia as a stress-evoked sympathetically maintained neuropathic pain syndrome and proposes dorsal root ganglia as the key neural hubs were different infective, autoimmune, and/or psychological stressors could be converted in neuropathic pain.

This model has been backed by the following lines of investigation: Dorsal root ganglia contains the small nerve fiber nuclei, each individual nucleus is tightly enveloped by immune-competent glial cells. About half of fibromyalgia patients have skin biopsy–proven small fiber neuropathy.

One study found a tight clinical-pathological correlation between corneal nerve fiber damage and small fiber neuropathy symptoms in fibromyalgia patients, after excluding cases with concomitant severe anxiety/depression.

The ion channel (Nav1.7) plays a major role in the pain electric signaling within the dorsal root ganglia. Severe fibromyalgia is associated with a particular Nav1.7 genotype.

After exercise, patients with ME/CFS and comorbid fibromyalgia displayed greater increases than controls in gene expression for metabolites detecting dorsal root ganglia sensory receptors including acid-sensing ion channel 3 and P2X purinoreceptors 4 and 5. Immunoglobulin G derived from fibromyalgia patients induces hyperalgesia and peripheral denervation in mice; such immunoglobulin G is specifically deposited in the mice dorsal root ganglia. Similarly, neutrophils from fibromyalgia patients induce hyperalgesia and dorsal root ganglia inflammation in mice.

Once in the dorsal root ganglia, SARS-Cov-2 or its transcripts may induce an immune-mediated inflammation; the mounted response could affect small nerve fibers nuclei with the resulting small fiber neuropathy manifested as chronic pain and dysautonomia. This different model is a hypothesis-generating construct that should be tested with the appropriate animal and clinical studies.