Reduced Presynaptic Dopamine Activity in Fibromyalgia Syndrome Demonstrated With Positron Emission Tomography: A Pilot Study

Department of Family Medicine and Anesthesiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71103, USA.
Journal of Pain (Impact Factor: 4.01). 02/2007; 8(1):51-8. DOI: 10.1016/j.jpain.2006.05.014
Source: PubMed


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.

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Available from: John Sunderland, Sep 09, 2014
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    • "In contrast, in patients with schizophrenia, an insensitivity to pain has been documented early [10] and confirmed in more recent experimental studies [11], [12]. Further evidence for a dopaminergic influence on pain perception derives from observations of altered dopaminergic neurotransmission in various chronic pain conditions [13]–[16]. In addition, small clinical studies indicated that dopaminergic agents can relieve chronic pain [17]–[19]. "
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    ABSTRACT: Pain is a multidimensional experience, which includes sensory, cognitive, and affective aspects. Converging lines of evidence indicate that dopaminergic neurotransmission plays an important role in human pain perception. However, the precise effects of dopamine on different aspects of pain perception remain to be elucidated. To address this question, we experimentally decreased dopaminergic neurotransmission in 22 healthy human subjects using Acute Phenylalanine and Tyrosine Depletion (APTD). During APTD and a control condition we applied brief painful laser stimuli to the hand, assessed different aspects of pain perception, and recorded electroencephalographic responses. APTD-induced decreases of cerebral dopaminergic activity did not influence sensory aspects of pain perception. In contrast, APTD yielded increases of pain unpleasantness. The increases of unpleasantness ratings positively correlated with effectiveness of APTD. Our finding of an influence of dopaminergic neurotransmission on affective but not sensory aspects of phasic pain suggests that analgesic effects of dopamine might be mediated by indirect effects on pain affect rather than by direct effects on ascending nociceptive signals. These findings contribute to our understanding of the complex relationship between dopamine and pain perception, which may play a role in various clinical pain states.
    PLoS ONE 04/2014; 9(4):e96167. DOI:10.1371/journal.pone.0096167 · 3.23 Impact Factor
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    • "FM patients have been shown to present structural differences in the brain [14] [20]. Furthermore, there are several evidences of central sensitization at various levels in the nervous system [12], as well as neurochemical imbalances in the central nervous system leading to a central amplification of pain perception [15] [46]. "
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    ABSTRACT: Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control females (Illumina 630k array) was obtained for genome-wide association scan (GWAS) analysis. Copy number variants (CNV) in FM susceptibility were analysed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2x400k platform. No SNP reached GWAS association threshold, but 21 of the most associated single nucleotide polymorphisms (SNPs) were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (p = 4.28x10(-5), OR (95%CI) = 0.58 (0.44-0.75)). aCGH detected five differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 showed to be associated to female cases of FM with low levels of comorbidities (p = 0.021, OR (95%CI) = 1.46 (1.05-2.04)). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies this would highlight a neurocognitive involvement in agreement with latest reports.
    Pain 02/2014; 155(6). DOI:10.1016/j.pain.2014.02.016 · 5.21 Impact Factor
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    • "FMS patients show an augmented prolactin response to a buspirone challenge test, suggesting an increased sensitivity or density of dopamine D2 receptors [29]. Positron emission tomography L-DOPA uptake studies also implicate disrupted presynaptic dopamine activities [30]. "
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    ABSTRACT: Fibromyalgia syndrome (FMS) is a common chronic musculoskeletal pain disorder of unknown etiology and characterized by generalized body pain, hyperalgesia, and other functional and emotional comorbidities. Despite extensive research, no treatment modality is effective for all FMS patients. In this paper, we briefly review the history of FMS and diagnostic criteria, and potential pathophysiological mechanisms including central pain modulation, neurotransmitters, sympatho-adrenal and hypothalamic-pituitary-adrenal systems and peripheral muscle issues. The primary focus of the paper is to review treatment options for managing fibromyalgia symptoms. We will discuss FDA-approved medications and other pharmacologic agents, and non-pharmacologic treatments that have shown promising effects.
    12/2013; 2(2):87-104. DOI:10.1007/s40122-013-0016-9
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