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.

Keywords: Dorsal root ganglia; Fibromyalgia; Myalgic encephalomyelitis/chronic fatigue syndrome; Small fiber neuropathy; Sodium channels.

Fig. 1

a Micrograph section of a thoracic human dorsal root ganglia in higher magnification showing neuronal nuclei of different sizes in the periphery of DRG, next to the thick connective tissue covering. b Schematic representation of the micrograph figure highlighting the variety of different structures and cell types in human dorsal root ganglia. 1 = connective tissue layers, 2 = fibroblasts, 3 = capillaries, 4 = basement membran, 5 = nerve, 6 = satellite glial cells, 7 = pseudo-unipolar process originating from sensory neurons with prominent nuclei containing a singular nucleolus (8) and sometimes lipofuszin (9). 10 = Non-neuronal cells including T and B lymphocytes and macrophages (11). Reproduced from Haberberger et al. Human dorsal root ganglia [6]. This open access publication explicitely allows reproduction of the figures providing the appropiate credit is given