Dorsal root ganglia, sodium channels, and fibromyalgia sympathetic pain.
Fibromyalgia (FM) is the most frequent cause of generalized pain in the community. Trauma and infection are frequent FM triggering events. A consistent line of investigation suggests that autonomic dysfunction may explain the multi-system features of FM, and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are potential sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7) act as molecular gatekeepers of pain detection at peripheral nociceptors. Different infecting agents may lie dormant in DGR. Trauma or infection can induce neuroplasticity with an over-expression of sympathetic fibers and sodium channels in DRG. Nerve growth factor (NGF) mediates these phenotypic changes, which enable catecholamines and/or sympathetic impulses to activate nociceptors. Several DRG sodium "channelopathies" have been recently associated to rare painful-dysautonomic syndromes, such as primary erythermalgia and paroxysmal extreme pain disorder (formerly familial rectal pain syndrome). We propose that enhanced DRG excitability may play a key role in FM pain. Individuals at risk would be those with genetically determined sympathetic hyperactivity, or those with inherent sodium channelopathies. Today's stressful environment may contribute to permanent sympathetic hyperactivity. Trauma or infection would induce sodium channels up-regulation and sympathetic sprouting in DRG through NGF over-expression. High levels of NGF have been reported in the cerebro-spinal fluid of FM patients. These post-traumatic (or post-infective) phenotypic changes would induce a sympathetically maintained neuropathic pain syndrome resulting in widespread pain, allodynia and paresthesias - precisely, the key clinical features of FM. If this hypothesis proves to be true, then sodium channel blockers could become therapeutic options for FM pain.
National Institute of Cardiology, Rheumatology Department, Juan Badiano 1, 14080 Mexico City, Mexico. mmlavin@infosel.net.mx
Manuel
M
Martinez-Lavin
Carla
C
Solano
D053447:Channelopathies / Q000503:physiopathology; D005356:Fibromyalgia / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000503:physiopathology*; D006801:Humans; D008959:Models, Neurological; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013577:Syndrome
D015222:Sodium Channels