Localized 1H-NMR Spectroscopy in Patients with Fibromyalgia: a Controlled Study of Changes in Cerebral Glutamate/glutamine, Inositol, Choline, and N-acetylaspartate

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2010 Jul 9

PMID 20609227

Citations 45

Authors

Nicolas Fayed

Javier Garcia-Campayo

Rosa Magallon

Helena Andres-Bergareche

Juan V Luciano

Eva Andres

Julian Beltran

Affiliations

Soon will be listed here.

Abstract

Introduction: The purpose of this study was to investigate whether single-voxel (SV) proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) detected differences between fibromyalgia (FM) patients and healthy controls. We also searched for correlations between neuroimaging abnormalities and neuropsychological variables.

Methods: Ten patients with FM and 10 gender- and age-matched control subjects were studied. A neuropsychological examination, DWI, DTI, and proton MRS were performed on the brain areas known to be associated with pain processing.

Results: Compared with healthy controls, FM patients had significantly higher levels of glutamate + glutamine (Glx) (mean ± SD, 10.71 ± 0.50 arbitrary institutional units versus 9.89 ± 1.04; P = 0.049) and higher glutamate + glutamine/creatine (Glx/Cr) ratios (1.90 ± 0.12 versus 1.72 ± 0.23; P = 0.034) in the posterior gyrus. Myoinositol (Ins) levels of the right and left hippocampi were significantly lower in FM patients (4.49 ± 0.74 versus 5.17 ± 0.62; P = 0.008 and 4.91 ± 0.85 versus 6.09 ± 0.78; P = 0.004, respectively). In FM patients, decreased myoinositol/creatine (Ins/Cr) ratios were found in the left sensorimotor area (P = 0.05) and the left hippocampus (P = 0.002) and lower levels of choline (P = 0.019) and N-acetyl aspartate + N-acetyl aspartyl glutamate (NAA + NAG) (P = 0.034) in the left hippocampus. Significant correlations between depression, pain, and global function and the posterior gyrus Glx levels and Glx/Cr ratios were observed.

Conclusions: Glx within the posterior gyrus could be a pathologic factor in FM. Hippocampal dysfunction may be partially responsible for the depressive symptoms of FM. Additional studies with larger samples are required to confirm these preliminary data.

Citing Articles

Serum choline, leptin and interleukin-6 levels in fibromyalgia syndrome-induced pain: a case-control study.

Baris E, Topaloglu I, Akalin E, Hamurtekin E, Kabaran S, Gelal A BMC Musculoskelet Disord. 2025; 26(1):97.

PMID: 39893410 PMC: 11786483. DOI: 10.1186/s12891-025-08337-0.

What has brain diffusion magnetic resonance imaging taught us about chronic primary pain: a narrative review.

Bautin P, Fortier M, Sean M, Little G, Martel M, Descoteaux M Pain. 2025; 166(2):243-261.

PMID: 39793098 PMC: 11726505. DOI: 10.1097/j.pain.0000000000003345.

Neuroimaging and artificial intelligence for assessment of chronic painful temporomandibular disorders-a comprehensive review.

Shrivastava M, Ye L Int J Oral Sci. 2023; 15(1):58.

PMID: 38155153 PMC: 10754947. DOI: 10.1038/s41368-023-00254-z.

Pain Biomarkers in Fibromyalgia Syndrome: Current Understanding and Future Directions.

Favretti M, Iannuccelli C, Di Franco M Int J Mol Sci. 2023; 24(13).

PMID: 37445618 PMC: 10341963. DOI: 10.3390/ijms241310443.

Orally Administered Bifidobacterium adolescentis Diminishes Serum Glutamate Concentration in Mice.

Royo F, Tames H, Bordanaba-Florit G, Cabrera D, Azparren-Angulo M, Garcia-Vallicrosa C Microbiol Spectr. 2023; 11(4):e0506322.

PMID: 37347184 PMC: 10433951. DOI: 10.1128/spectrum.05063-22.

References

Harwood A . Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited. Mol Psychiatry. 2004; 10(1):117-26. DOI: 10.1038/sj.mp.4001618. View

Ogura A, Miyamoto M, Kudo Y . Neuronal death in vitro: parallelism between survivability of hippocampal neurones and sustained elevation of cytosolic Ca2+ after exposure to glutamate receptor agonist. Exp Brain Res. 1988; 73(3):447-58. DOI: 10.1007/BF00406601. View

Garcia-Campayo J, Fayed N, Serrano-Blanco A, Roca M . Brain dysfunction behind functional symptoms: neuroimaging and somatoform, conversive, and dissociative disorders. Curr Opin Psychiatry. 2009; 22(2):224-31. DOI: 10.1097/YCO.0b013e3283252d43. View

Cordoba J, Sanpedro F, Alonso J, Rovira A . 1H magnetic resonance in the study of hepatic encephalopathy in humans. Metab Brain Dis. 2003; 17(4):415-29. DOI: 10.1023/a:1021926405944. View

Gracely R, Petzke F, Wolf J, Clauw D . Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002; 46(5):1333-43. DOI: 10.1002/art.10225. View

Kwiatek R, Barnden L, Tedman R, Jarrett R, Chew J, Rowe C . Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami. Arthritis Rheum. 2001; 43(12):2823-33. DOI: 10.1002/1529-0131(200012)43:12<2823::AID-ANR24>3.0.CO;2-E. View

Cook D, Lange G, Ciccone D, Liu W, Steffener J, Natelson B . Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol. 2004; 31(2):364-78. View

Provencher S . Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993; 30(6):672-9. DOI: 10.1002/mrm.1910300604. View

Dickenson A . Gate control theory of pain stands the test of time. Br J Anaesth. 2002; 88(6):755-7. DOI: 10.1093/bja/88.6.755. View

10.

Wood P, Ledbetter C, Glabus M, Broadwell L, Patterson 2nd J . Hippocampal metabolite abnormalities in fibromyalgia: correlation with clinical features. J Pain. 2008; 10(1):47-52. DOI: 10.1016/j.jpain.2008.07.003. View

11.

Harris R, Sundgren P, Pang Y, Hsu M, Petrou M, Kim S . Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. Arthritis Rheum. 2008; 58(3):903-7. DOI: 10.1002/art.23223. View

12.

Wolfe F . Fibromyalgia: the clinical syndrome. Rheum Dis Clin North Am. 1989; 15(1):1-18. View

13.

McKenna J, Melzack R . Blocking NMDA receptors in the hippocampal dentate gyrus with AP5 produces analgesia in the formalin pain test. Exp Neurol. 2001; 172(1):92-9. DOI: 10.1006/exnr.2001.7777. View

14.

Sundgren P, Petrou M, Harris R, Fan X, Foerster B, Mehrotra N . Diffusion-weighted and diffusion tensor imaging in fibromyalgia patients: a prospective study of whole brain diffusivity, apparent diffusion coefficient, and fraction anisotropy in different regions of the brain and correlation with symptom severity. Acad Radiol. 2007; 14(7):839-46. DOI: 10.1016/j.acra.2007.03.015. View

15.

Fayed N, Modrego P, Medrano J . Comparative test-retest reliability of metabolite values assessed with magnetic resonance spectroscopy of the brain. The LCModel versus the manufacturer software. Neurol Res. 2009; 31(5):472-7. DOI: 10.1179/174313209X395481. View

16.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

17.

Ross A, Sachdev P . Magnetic resonance spectroscopy in cognitive research. Brain Res Brain Res Rev. 2004; 44(2-3):83-102. DOI: 10.1016/j.brainresrev.2003.11.001. View

18.

Burckhardt C, Clark S, Bennett R . The fibromyalgia impact questionnaire: development and validation. J Rheumatol. 1991; 18(5):728-33. View

19.

Lobo A, Saz P, Marcos G, Dia J, de la Camara C, Ventura T . [Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-Mental Status Examination) in the general geriatric population]. Med Clin (Barc). 1999; 112(20):767-74. View

20.

Bosman D, Deutz N, De Graaf A, vd Hulst R, van Eijk H, Bovee W . Changes in brain metabolism during hyperammonemia and acute liver failure: results of a comparative 1H-NMR spectroscopy and biochemical investigation. Hepatology. 1990; 12(2):281-90. DOI: 10.1002/hep.1840120215. View