Tag: small nerve fibers

Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with a broad overlap of symptomatology with Post-COVID Syndrome (PCS). Despite the severity of symptoms and various neurological, cardiovascular, microvascular, and skeletal muscular findings, no biomarkers have been identified.

The Transient receptor potential melastatin 3 (TRPM3) channel, involved in pain transduction, thermosensation, transmitter and neuropeptide release, mechanoregulation, vasorelaxation, and immune defense, shows altered function in ME/CFS. Dysfunction of TRPM3 in natural killer (NK) cells, characterized by reduced calcium flux, has been observed in ME/CFS and PCS patients, suggesting a role in ineffective pathogen clearance and potential virus persistence and autoimmunity development.

TRPM3 dysfunction in NK cells can be improved by naltrexone in vitro and ex vivo, which may explain the moderate clinical efficacy of low-dose naltrexone (LDN) treatment. We propose that TRPM3 dysfunction may have a broader involvement in ME/CFS pathophysiology, affecting other organs. This paper discusses TRPM3’s expression in various organs and its potential impact on ME/CFS symptoms, with a focus on small nerve fibers and the brain, where TRPM3 is involved in presynaptic GABA release.

Source: Löhn M, Wirth KJ. Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone. J Transl Med. 2024 Jul 5;22(1):630. doi: 10.1186/s12967-024-05412-3. PMID: 38970055; PMCID: PMC11227206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227206/ (Full Text)

Dorsal root ganglia: fibromyalgia pain factory?

Abstract:

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.

Source: Martínez-Lavín M. Dorsal root ganglia: fibromyalgia pain factory? Clin Rheumatol. 2021 Jan 6:1–5. doi: 10.1007/s10067-020-05528-z. Epub ahead of print. PMID: 33409721; PMCID: PMC7787228.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787228/ (Full text)