Dorsal root ganglia: fibromyalgia pain factory?, 2021, Martinez-Lavin

Andy · Jan 8, 2021

This perspective article focuses on dorsal root ganglia (DRG) as potential fibromyalgia main pain source. Humans possess 31 pairs of DRG lying along the spine. These ganglia have unique anatomical and physiological features. During development, DRG are extruded from the central nervous system and from the blood-brain barrier but remain surrounded by meningeal layers and by cerebrospinal fluid.

DRG house the pain-transmitting small nerve fiber nuclei; each individual nucleus is tightly enveloped by metabolically active glial cells. DRG possess multiple inflammatory/pro-nociceptive molecules including ion channels, neuropeptides, lymphocytes, and macrophages. DRG neurons have pseudo-unipolar structure making them able to generate pain signals; additionally, they can sequester antigen-specific antibodies thus inducing immune-mediated hyperalgesia. In rodents, diverse physical and/or environmental stressors induce DRG phenotypic changes and hyperalgesia.

Unfolding clinical evidence links DRG pathology to fibromyalgia and similar syndromes. Severe fibromyalgia is associated to particular DRG ion channel genotype. Myalgic encephalomyelitis patients with comorbid fibromyalgia have exercise-induced DRG pro-nociceptive molecules gene overexpression. Skin biopsy demonstrates small nerve fiber pathology in approximately half of fibromyalgia patients.

A confocal microscopy study of fibromyalgia patients disclosed strong correlation between corneal denervation and small fiber neuropathy symptom burden. DRG may be fibromyalgia neural hub where different stressors can be transformed in neuropathic pain. Novel neuroimaging technology and postmortem inquest may better define DRG involvement in fibromyalgia and similar maladies. DRG pro-nociceptive molecules are attractive fibromyalgia therapeutic targets.

Significant advances in fibromyalgia knowledge have been gained in the last decade. The focus is being shifted from considering fibromyalgia a centralized pain syndrome to recognizing the role of autonomic and peripheral nociceptive nervous systems in the generation of widespread pain, fatigue, and insomnia. The description of small nerve fiber pathology in a sizable subgroup of fibromyalgia patients strongly supports the disease neuropathic-autonomic underpinning [1].

Fibromyalgia overlaps with other complex painful-dysautonomic syndromes including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome, gulf war illness, macrophagic myofasciitis, and post-HPV vaccination syndrome. These overlapping syndromes may have common underlying pathophysiology [2].

Fibromyalgia is clearly a stress-related disorder. Psychological distress, physical trauma, and/or autoimmune illnesses are frequent fibromyalgia drivers. Dorsal root ganglia (DRG) have unique anatomical and physiological features making them able to convert varied afferent stressful impulses, including psychological distress, into neuropathic pain [3].

Previous publications from our department discussed the potential role of DRG sodium channels in fibromyalgia pain [4, 5]. The objective of this communication is to examine DRG unique pro-nociceptive anatomy, physiology, and immune competence, as well as to analyze recent clinical and experimental evidence linking DRG physiopathology to fibromyalgia pain. The focus on DRG as potential fibromyalgia pain factory in no way disregards other pathogenic proposals. Discussion of other hypotheses is beyond the scope of this perspective article.
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Open access, https://link.springer.com/article/10.1007/s10067-020-05528-z

Edited to break up paragraphs for ease of reading.

MEMarge · Jan 8, 2021

Inflammation of the dorsal root ganglia have been found in autopsies of people with ME.

"Fibromyalgia is clearly a stress-related disorder. Psychological distress, physical trauma, and/or autoimmune illnesses are frequent fibromyalgia drivers. Dorsal root ganglia (DRG) have unique anatomical and physiological features making them able to convert varied afferent stressful impulses, including psychological distress, into neuropathic pain [3]."

The author's only reference for this is his unpublished work below:

3 Martínez-Lavín M (2020) Fibromyalgia in women: somatisation or stress-evoked, sex-dimorphic neuropathic pain? Clinical and experimental rheumatology. Advance online publication

ukxmrv · Jan 8, 2021

MEMarge said: ↑

Inflammation of the dorsal root ganglia have been found in autopsies of people with ME.

"Fibromyalgia is clearly a stress-related disorder. Psychological distress, physical trauma, and/or autoimmune illnesses are frequent fibromyalgia drivers. Dorsal root ganglia (DRG) have unique anatomical and physiological features making them able to convert varied afferent stressful impulses, including psychological distress, into neuropathic pain [3]."

The author's only reference for this is his unpublished work below:

3 Martínez-Lavín M (2020) Fibromyalgia in women: somatisation or stress-evoked, sex-dimorphic neuropathic pain? Clinical and experimental rheumatology. Advance online publication
Click to expand...

By some sort of magic?

Mithriel · Jan 9, 2021

Severe fibromyalgia is associated to particular DRG ion channel genotype. Myalgic encephalomyelitis patients with comorbid fibromyalgia have exercise-induced DRG pro-nociceptive molecules gene overexpression. Skin biopsy demonstrates small nerve fiber pathology in approximately half of fibromyalgia patients.
Click to expand...

I have never heard that ME has "exercise-induced DRG pro-nociceptive molecules gene overexpression"

Diagnosing FM and ME is very lax. One doctor said that the criteria for FM was now so loose it was almost meaningless and it in things like FND FM means widespread pain and CFS means fatigue.

When things are found in patients with FM and ME together I wonder how much effort they have made to distinguish the severe myalgia of fibromyalgia with the severe myalgia of ME.

Maybe work like this will eventually be a proper test for FM and lead to a treatment but it seems like a way to bring biology to "stress related"

I am more interested in treatments for dorsal ganglia problems because it has been found at autopsy in the few autopsies that have been done on people with ME.

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Dorsal root ganglia: fibromyalgia pain factory?, 2021, Martinez-Lavin

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