Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study.

UNLABELLED Although the pathophysiology underlying the pain of fibromyalgia syndrome (FMS) remains unknown, a variety of clinical and investigational findings suggests a dysregulation of dopaminergic neurotransmission. We therefore investigated presynaptic dopaminergic function in 6 female FMS patients in comparison to 8 age- and gender-matched controls as assessed by positron emission tomography with 6-[(18)F]fluoro-L-DOPA as a tracer. Semiquantitative analysis revealed reductions in 6-[(18)F]fluoro-L-DOPA uptake in several brain regions, indicating a disruption of presynaptic dopamine activity wherein dopamine plays a putative role in natural analgesia. Although the small sample size makes these findings preliminary, it appears that FMS might be characterized by a disruption of dopaminergic neurotransmission. PERSPECTIVE An association between FMS and reduced dopamine metabolism within the pain neuromatrix provides important insights into the pathophysiology of this mysterious disorder.

[1]  G. Gessa,et al.  The role of stress in the pathophysiology of the dopaminergic system , 2000, Molecular Psychiatry.

[2]  L. Arendt-Nielsen,et al.  Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients , 2000, Pain.

[3]  B. Orser,et al.  A D2 Class Dopamine Receptor Transactivates a Receptor Tyrosine Kinase to Inhibit NMDA Receptor Transmission , 2002, Neuron.

[4]  Alan C. Evans,et al.  Dopa decarboxylase activity of the living human brain. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. Grace,et al.  Chronic Cold Stress Reduces the Spontaneous Activity of Ventral Tegmental Dopamine Neurons , 2001, Neuropsychopharmacology.

[6]  J E Holden,et al.  Evaluation of Dopaminergic Presynaptic Integrity: 6-[18F]Fluoro-L-Dopa Versus 6-[18F]Fluoro-L-m-Tyrosine , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  K. Franklin,et al.  6-Hydroxydopamine lesions of the ventral tegmentum abolishd-amphetamine and morphine analgesia in the formalin test but not in the tail flick test , 1990, Brain Research.

[8]  J. Rinne Nigral degeneration in Parkinson's disease in relation to clinical features , 1991, Acta neurologica Scandinavica. Supplementum.

[9]  W. Weiner,et al.  Parkinson's Disease: Diagnosis and Clinical Management , 2007 .

[10]  E. Lauterbach The neuropsychiatry of Parkinson's disease and related disorders. , 2004, The Psychiatric clinics of North America.

[11]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[12]  Jason Steffener,et al.  Functional imaging of pain in patients with primary fibromyalgia. , 2004, The Journal of rheumatology.

[13]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

[14]  R. Takeda,et al.  Unilateral lesions of mesostriatal dopaminergic pathway alters the withdrawal response of the rat hindpaw to mechanical stimulation , 2005, Neuroscience Research.

[15]  A. López‐Avila,et al.  Lesion and electrical stimulation of the ventral tegmental area modify persistent nociceptive behavior in the rat , 2001, Brain Research.

[16]  Akinori Nakamura,et al.  Cognitive- and motor-related regions in Parkinson's disease: FDOPA and FDG PET studies , 2004, NeuroImage.

[17]  S. Jabbur,et al.  Augmentation of nociceptive reflexes and chronic deafferentation pain by chemical lesions of either dopaminergic terminals or midbrain dopaminergic neurons , 1997, Brain Research.

[18]  J. Rinne Nigral degeneration in parkinson's disease , 1993, Movement disorders : official journal of the Movement Disorder Society.

[19]  S. Kapur,et al.  NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors—implications for models of schizophrenia , 2002, Molecular Psychiatry.

[20]  N. Chater The Search for Simplicity: A Fundamental Cognitive Principle? , 1999 .

[21]  N. Castro,et al.  Direct inhibition of the N‐methyl‐D‐aspartate receptor channel by dopamine and (+)‐SKF38393 , 1999, British journal of pharmacology.

[22]  Leslie J Crofford,et al.  Memory beliefs and function in fibromyalgia patients. , 2005, Journal of psychosomatic research.

[23]  C. Singer Urinary dysfunction in Parkinson's disease. , 1998, Clinical neuroscience.

[24]  R. Melzack,et al.  Blocking NMDA Receptors in the Hippocampal Dentate Gyrus with AP5 Produces Analgesia in the Formalin Pain Test , 2001, Experimental Neurology.

[25]  P. Keck,et al.  Comorbidity of fibromyalgia with medical and psychiatric disorders. , 1992, The American journal of medicine.

[26]  G. Kirouac,et al.  Cardiovascular depressor responses to stimulation of substantia nigra and ventral tegmental area. , 1997, The American journal of physiology.

[27]  T. Rammsayer,et al.  Neuropharmacological Evidence for Different Timing Mechanisms in Humans , 1999, The Quarterly journal of experimental psychology. B, Comparative and physiological psychology.

[28]  M. Gill,et al.  Dopaminergic System Genes in ADHD: Toward a Biological Hypothesis , 2002, Neuropsychopharmacology.

[29]  P. Tugwell,et al.  The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. , 1990, Arthritis and rheumatism.

[30]  H. Ursin,et al.  Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls. , 2003, Journal of affective disorders.

[31]  Karl J. Friston,et al.  A unified statistical approach for determining significant signals in images of cerebral activation , 1996, Human brain mapping.

[32]  B. Shyu,et al.  Neurophysiological, pharmacological and behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia , 1992, Brain Research.

[33]  A Dagher,et al.  Functional Imaging in Parkinson's Disease , 2001, Seminars in neurology.

[34]  C. Vierck,et al.  Effects of the N-methyl-D-aspartate receptor antagonist dextromethorphan on temporal summation of pain are similar in fibromyalgia patients and normal control subjects. , 2005, The journal of pain : official journal of the American Pain Society.

[35]  A. Holman,et al.  A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. , 2005, Arthritis and rheumatism.

[36]  R M Bennett,et al.  The fibromyalgia impact questionnaire: development and validation. , 1991, The Journal of rheumatology.

[37]  Daniel J Clauw,et al.  Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. , 2002, Arthritis and rheumatism.

[38]  B. Ford Pain in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[39]  Juha O. Rinne,et al.  Cortical 6-[18F]fluoro-l-dopa uptake and frontal cognitive functions in early Parkinson's disease , 2005, Neurobiology of Aging.

[40]  L. Descarries,et al.  Comparative analysis of the effects of iontophoretically applied dopamine in different regions of the rat brain, with special reference to the cingulate cortex , 1991, Synapse.

[41]  P. Seeman,et al.  Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics , 2005, Molecular Psychiatry.

[42]  C Nahmias,et al.  Cerebral Metabolism of 6–[18F]Fluoro‐l‐3,4‐Dihydroxyphenylalanine in the Primate , 1987, Journal of neurochemistry.

[43]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[44]  L. Jasmin,et al.  Dopaminergic input to GABAergic neurons in the rostral agranular insular cortex of the rat , 2003, Journal of neurocytology.

[45]  C. Tanner,et al.  Pain in Parkinson's disease , 1986, Movement disorders : official journal of the Movement Disorder Society.

[46]  P. Nathan,et al.  The pharmacology of human working memory. , 2001, The international journal of neuropsychopharmacology.

[47]  P. Wood Stress and dopamine: implications for the pathophysiology of chronic widespread pain. , 2004, Medical hypotheses.

[48]  A. Bengtsson,et al.  Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. , 1995, Scandinavian journal of rheumatology.

[49]  J. Stewart,et al.  The role of dopamine in the nucleus accumbens in analgesia. , 1999, Life sciences.

[50]  M. Zhuo,et al.  Descending facilitatory modulation of a behavioral nociceptive response by stimulation in the adult rat anterior cingulate cortex , 2000, European journal of pain.

[51]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[52]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[53]  A. López‐Avila,et al.  Dopamine and NMDA systems modulate long-term nociception in the rat anterior cingulate cortex , 2004, Pain.

[54]  W. Poewe,et al.  Akathisia, restless legs and periodic limb movements in sleep in Parkinson’s disease , 2004, Neurology.

[55]  A. Bengtsson,et al.  Fibromyalgia--are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs. , 1997, The Journal of rheumatology.

[56]  W. Jost,et al.  Constipation in idiopathic Parkinson's disease. , 2003, Scandinavian journal of gastroenterology.

[57]  Monique Ernst,et al.  DOPA Decarboxylase Activity in Attention Deficit Hyperactivity Disorder Adults. A [Fluorine-18]Fluorodopa Positron Emission Tomographic Study , 1998, The Journal of Neuroscience.

[58]  W. Jost Autonomic dysfunctions in idiopathic Parkinson's disease , 2003, Journal of Neurology.

[59]  W. Fogel,et al.  Restless legs syndrome—new insights into clinical characteristics, pathophysiology, and treatment options , 2004, Journal of Neurology.

[60]  J. Rinne,et al.  Role of the dopaminergic system in chronic pain – a fluorodopa-PET study , 2001, Pain.

[61]  Kjell Någren,et al.  Altered dopamine D2 receptor binding in atypical facial pain , 2003, Pain.

[62]  I. Russell,et al.  Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. , 1992, Arthritis and rheumatism.

[63]  E. Legangneux,et al.  Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin and [3H]imipramine reuptake in the primary fibromyalgia syndrome. , 2001, Rheumatology.

[64]  L. Jasmin,et al.  Dopamine Reuptake Inhibition in the Rostral Agranular Insular Cortex Produces Antinociception , 1999, The Journal of Neuroscience.

[65]  I. Russell,et al.  Fibromyalgia Syndrome: Canadian Clinical Working Case Definition, Diagnostic and Treatment Protocols–A Consensus Document , 2003, The Fibromyalgia Syndrome: A Clinical Case Definition for Practitioners.