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.

Is fibromyalgia an autoimmune illness?

“…Goebel et al's provocative study supports our reiterated proposal of DRG as the key neural hub where different fibromyalgia-inducing stressors, including autoimmune illnesses, are converted into neuropathic pain [14,17,18].…”

“…DRG phenotypic changes can also explain fibromyalgia dysautonomia-related symptoms including chronic fatigue and irritable bowel. There is direct anatomical communication between DRG and the paravertebral sympathetic chain [14]. DRG mechanosensitive neurons projecting to distal blood vessels seem to play a major role in cardiovascular autonomic regulation [15].…”

Analgesia effect of lentivirus-siSCN9A infected neurons in vincristine induced neuropathic pain rats

“…DRG plays an extremely important role in neuroprotection, nerve injury, repair and extension of nerve axons in vitro, and the influence of noxious stimuli such as heat and pain on ion channels and other related biological experiments and pharmacological research [ 39 ]. In DRG neurons, voltage-gated sodium channels play an important role in the occurrence of pain.…”

Adult mouse dorsal root ganglia neurons form aberrant glutamatergic connections in dissociated cultures

“…Functional and structural synapse formation and network development potential of sensory neurons may explain neuronto-neuron interactions in a new scope [3]. These findings may shed new light on various disorders such as neuropathies, fibromyalgia, small fiber neuropathy, immune-mediated hyperalgesia, and other pain syndromes of peripheral nervous system [42,43].…”