Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Dorsal root ganglia, sodium channels, and fibromyalgia sympathetic pain. 1884 1

Many scientists are seeking better therapies for treating fibromyalgia (FM) pain. We used a mouse model of FM to determine if ASIC3 and its relevant signaling pathway participated in FM pain. We demonstrated that FM-induced mechanical hyperalgesia was attenuated by electroacupuncture (EA). The decrease in fatigue-induced lower motor function in FM mice was also reversed by EA. These EA-based effects were abolished by the opioid receptor antagonist naloxone and the adenosine A1 receptor antagonist rolofylline. Administration of opioid receptor agonist endomorphin (EM) or adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) has similar results to EA. Similar results were also observed in ASIC3-/- or ASIC3 antagonist (APETx2) injected mice. Using western blotting, we determined that pPKA, pPI3K, and pERK were increased during a dual acidic injection priming period. Nociceptive receptors, such as ASIC3, Nav1.7, and Nav1.8, were upregulated in the dorsal root ganglion (DRG) and spinal cord (SC) of FM mice. Furthermore, pPKA, pPI3K, and pERK were increased in the central thalamus. These aforementioned mechanisms were completely abolished in ASIC3 knockout mice. Electrophysiological results also indicated that acid potentiated Nav currents through ASIC3 and ERK pathway. Our results highlight the crucial role of ASIC3-mediated mechanisms in the treatment of FM-induced mechanical hyperalgesia.
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PMID:Targeting ASIC3 for Relieving Mice Fibromyalgia Pain: Roles of Electroacupuncture, Opioid, and Adenosine. 2844 Feb 80