title: A reconsideration of the relevance of systemic low-dose ketamine to the pathophysiology of fibromyalgia.
abstract: Fibromyalgia is a common disorder characterized by chronic widespread pain that affects an estimated 2% of the general population. Recent advances have shed insight on this mysterious disorder, leading to the growing conclusion that disturbances of pain-related processes within the central nervous system, termed central sensitization, represent its most likely source. The phenomenon of central sensitization depends on plasticity in function of N-methyl-D-aspartate (NMDA) subtype glutamate receptors. Earlier studies implicated increased sensitivity of central NMDA receptors as playing a primary role in fibromyalgia, as evidenced by a significant reduction in symptoms among a large subset of patients in response to low doses of ketamine, a noncompetitive NMDA receptor antagonist. However, recent insights into the pharmacology of this drug cast doubt on a direct contribution of NMDA receptors and add credence to a model of the disorder that suggests that the primary pathology of fibromyalgia is a suppression of the normal activity of dopamine-releasing neurons within the limbic system. The implications for future therapies for fibromyalgia, and indeed many other chronic pain conditions, are discussed in light of these insights.
  
  
  CONCLUSIONS
  The current lack of a demonstrable pathology underlying the pain of fibromyalgia has hampered progress toward adequate treatment of this mysterious disorder. Accumulating evidence suggests that fibromyalgia may represent a dysregulation of dopaminergic neurotransmission, which may provide insights to guide both rational clinical interventions as well as system-specific research models.
authors.affiliation: Centre for Research on Pain, McGill University, Montreal, Quebec, Canada. pwood@isuhsc.edu
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Wood
mesh_terms: D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005356:Fibromyalgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009619:Nociceptors / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D004298:Dopamine