CoChat
Sign Up
Cited by 71Fibromyalgia and Chronic Fatigue Syndrome ResearchPain Mechanisms and TreatmentsMicroRNA in disease regulation

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome

Leinders, Mathias, Doppler, Kathrin, Klein, Thomas, Deckart, Maximiliane, Rittner, Heike, Sommer, Claudia, Üçeyler, Nurcan·2016·Pain
DOI 10.1097/j.pain.0000000000000668
Open this paper in CoChat — free account

Abstract

Fibromyalgia syndrome (FMS) is a chronic widespread pain condition probably comprising subgroups with different underlying pathomechanisms. There is increasing evidence for small nerve fiber impairment in subgroups of patients with FMS. MicroRNAs (miRNAs) regulate molecular factors determining nerve de- and re-generation. We investigated whether systemic and cutaneous miRNA expression in patients with FMS is related to small nerve fiber pathology. We confirmed previous findings of disturbed small fiber function and reduced intraepidermal nerve fiber density in subgroups of patients with FMS. We found 51 aberrantly expressed miRNAs in white blood cells of patients with FMS, of which miR-let-7d correlated with reduced small nerve fiber density in patients with FMS. Furthermore, we demonstrated miR-let-7d and its downstream target insulin-like growth factor-1 receptor as being aberrantly expressed in skin of patients with FMS with small nerve fiber impairment. Our study gives further evidence of small nerve fiber pathology in FMS subgroups and provides a missing link in the pathomechanism that may lead to small fiber loss in subgroups of patients with FMS.

Overview

Integrity signals

Registry

Crossref · 10.1097/j.pain.0000000000000668

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 1 references

Research works printed but not linked: 92

  1. Aldrich, 2009, Changes in expression of sensory organ-specific microRNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation, Neuroscience, 164, 711, 10.1016/j.neuroscience.2009.08.033 · DOI
  2. Bai, 2007, Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain, Mol Pain, 3, 15, 10.1186/1744-8069-3-15 · DOI
  3. Bao, 2013, Let-7 in cardiovascular diseases, heart development and cardiovascular differentiation from stem cells, Int J Mol Sci, 14, 23086, 10.3390/ijms141123086 · DOI
  4. Bennett, 2002, Adult growth hormone deficiency in patients with fibromyalgia, Curr Rheumatol Rep, 4, 306, 10.1007/s11926-002-0039-4 · DOI
  5. Bennett, 1997, Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia, J Rheumatol, 24, 1384
  6. Betel, 2008, The microRNA.org resource: targets and expression, Nucleic Acids Res, 36, D149
  7. Beyer, 2015, Signature of circulating microRNAs in osteoarthritis, Ann Rheum Dis, 74, e18, 10.1136/annrheumdis-2013-204698 · DOI
  8. Bjersing, 2015, Profile of circulating microRNAs in fibromyalgia and their relation to symptom severity: an exploratory study, Rheumatol Int, 35, 635, 10.1007/s00296-014-3139-3 · DOI
  9. Bjersing, 2013, Profile of cerebrospinal microRNAs in fibromyalgia, PLoS One, 8, e78762, 10.1371/journal.pone.0078762 · DOI · Paper page
  10. Bolstad, 2003, A comparison of normalization methods for high density oligonucleotide array data based on variance and bias, Bioinformatics, 19, 185, 10.1093/bioinformatics/19.2.185 · DOI
  11. Bote, 2013, Fibromyalgia: anti-inflammatory and stress responses after acute moderate exercise, PLoS One, 8, e74524, 10.1371/journal.pone.0074524 · DOI
  12. Bouhassira, 2004, Development and validation of the neuropathic pain symptom Inventory, PAIN, 108, 248, 10.1016/j.pain.2003.12.024 · DOI · Paper page
  13. Burckhardt, 1991, The fibromyalgia impact questionnaire: development and validation, J Rheumatol, 18, 728
  14. Caro, 2014, Evidence of abnormal epidermal nerve fiber density in fibromyalgia: clinical and immunologic implications, Arthritis Rheumatol, 66, 1945, 10.1002/art.38662 · DOI · Paper page
  15. Cerda-Olmedo, 2015, Identification of a microRNA signature for the diagnosis of fibromyalgia, PLoS One, 10, e0121903, 10.1371/journal.pone.0121903 · DOI
  16. Chou, 2016, miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database, Nucleic Acids Res, 44, D239, 10.1093/nar/gkv1258 · DOI
  17. Chudin, 2006, A model of technical variation of microarray signals, J Comput Biol, 13, 996, 10.1089/cmb.2006.13.996 · DOI
  18. Ciccacci, 2014, Common polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes, Acta Diabetol, 51, 663, 10.1007/s00592-014-0582-2 · DOI
  19. Clauw, 2015, Fibromyalgia and related conditions, Mayo Clin Proc, 90, 680, 10.1016/j.mayocp.2015.03.014 · DOI · Paper page
  20. Cuatrecasas, 2010, High prevalence of growth hormone deficiency in severe fibromyalgia syndromes, J Clin Endocrinol Metab, 95, 4331, 10.1210/jc.2010-0061 · DOI
  21. de Tommaso, 2014, Update on laser-evoked potential findings in fibromyalgia patients in light of clinical and skin biopsy features, J Neurol, 261, 461, 10.1007/s00415-013-7211-9 · DOI · Paper page
  22. Doppler, 2015, Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia, PAIN, 156, 2319, 10.1097/j.pain.0000000000000285 · DOI · Paper page
  23. Drummond, 2011, Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis, Physiol Genomics, 43, 595, 10.1152/physiolgenomics.00148.2010 · DOI
  24. 2010, European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society, J Peripher Nerv Syst, 15, 79, 10.1111/j.1529-8027.2010.00269.x · DOI
  25. English, 2003, Cytokines, growth factors and sprouting at the neuromuscular junction, J Neurocytol, 32, 943, 10.1023/B:NEUR.0000020634.59639.cf · DOI
  26. Esteller, 2011, Non-coding RNAs in human disease, Nat Rev Genet, 12, 861, 10.1038/nrg3074 · DOI · Paper page
  27. Favereaux, 2011, Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain, EMBO J, 30, 3830, 10.1038/emboj.2011.249 · DOI
  28. Forman, 2008, A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence, Proc Natl Acad Sci U S A, 105, 14879, 10.1073/pnas.0803230105 · DOI · Paper page
  29. Friedman, 2009, Most mammalian mRNAs are conserved targets of microRNAs, Genome Res, 19, 92, 10.1101/gr.082701.108 · DOI · Paper page
  30. Gao, 1999, IGF-I deficient mice show reduced peripheral nerve conduction velocities and decreased axonal diameters and respond to exogenous IGF-I treatment, J Neurobiol, 39, 142, 10.1002/(SICI)1097-4695(199904)39:1<142::AID-NEU11>3.0.CO;2-H · DOI
  31. Giannoccaro, 2014, Small nerve fiber involvement in patients referred for fibromyalgia, Muscle Nerve, 49, 757, 10.1002/mus.24156 · DOI · Paper page
  32. Gilam, 2013, Involvement of IGF-1R regulation by miR-515-5p modifies breast cancer risk among BRCA1 carriers, Breast Cancer Res Treat, 138, 753, 10.1007/s10549-013-2502-5 · DOI
  33. Griffiths-Jones, 2004, The microRNA Registry, Nucleic Acids Res, 32, D109, 10.1093/nar/gkh023 · DOI
  34. Hansson, 1988, Immunohistochemical localization of insulin-like growth factor I in the adult rat, Histochemistry, 89, 403, 10.1007/BF00500644 · DOI
  35. Hauser, 2008, What are the key symptoms of fibromyalgia? Results of a survey of the German Fibromyalgia Association [in German], Schmerz, 22, 176
  36. Hayashi, 2004, Sequence of IGF-I, IGF-II, and HGF expression in regenerating skeletal muscle, Histochem Cell Biol, 122, 427, 10.1007/s00418-004-0704-y · DOI
  37. He, 2010, Regulation of opioid tolerance by let-7 family microRNA targeting the mu opioid receptor, J Neurosci, 30, 10251, 10.1523/JNEUROSCI.2419-10.2010 · DOI
  38. Hsu, 2011, miRTarBase: a database curates experimentally validated microRNA-target interactions, Nucleic Acids Res, 39, D163, 10.1093/nar/gkq1107 · DOI
  39. Huttenhofer, 2006, The principles of guiding by RNA: chimeric RNA-protein enzymes, Nat Rev Genet, 7, 475, 10.1038/nrg1855 · DOI
  40. Ide, 1996, Peripheral nerve regeneration, Neurosci Res, 25, 101, 10.1016/0168-0102(96)01042-5 · DOI
  41. Iida, 2004, Muscle mechano growth factor is preferentially induced by growth hormone in growth hormone-deficient lit/lit mice, J Physiol, 560, 341, 10.1113/jphysiol.2004.069500 · DOI
  42. Imai, 2011, Change in microRNAs associated with neuronal adaptive responses in the nucleus accumbens under neuropathic pain, J Neurosci, 31, 15294, 10.1523/JNEUROSCI.0921-11.2011 · DOI
  43. Ishii, 1994, Role of insulin-like growth factors in peripheral nerve regeneration, Pharmacol Ther, 62, 125, 10.1016/0163-7258(94)90007-8 · DOI
  44. Jiang, 2010, MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells, Biochem J, 432, 199, 10.1042/BJ20100859 · DOI
  45. Jung, 2014, Regulation of IGF -1 signaling by microRNAs, Front Genet, 5, 472
  46. Kanje, 1989, Insulin-like growth factor I (IGF-I) stimulates regeneration of the rat sciatic nerve, Brain Res, 486, 396, 10.1016/0006-8993(89)90531-3 · DOI
  47. Kiryakova, 2010, Recovery of whisking function promoted by manual stimulation of the vibrissal muscles after facial nerve injury requires insulin-like growth factor 1 (IGF-1), Exp Neurol, 222, 226, 10.1016/j.expneurol.2009.12.031 · DOI
  48. Kosmidis, 2014, Reduction of Intraepidermal Nerve Fiber Density (IENFD) in the skin biopsies of patients with fibromyalgia: a controlled study, J Neurol Sci, 347, 143, 10.1016/j.jns.2014.09.035 · DOI · Paper page
  49. Kress, 2013, MicroRNAs in nociceptive circuits as predictors of future clinical applications, Front Mol Neurosci, 6, 33, 10.3389/fnmol.2013.00033 · DOI
  50. Kumar, 2013, Circulating miRNA biomarkers for Alzheimer's disease, PLoS One, 8, e69807, 10.1371/journal.pone.0069807 · DOI
  51. Kusuda, 2011, Differential expression of microRNAs in mouse pain models, Mol Pain, 7, 17, 10.1186/1744-8069-7-17 · DOI
  52. Lauria, 2005, EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, Eur J Neurol, 12, 747, 10.1111/j.1468-1331.2005.01260.x · DOI
  53. Lehmann, 2012, An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration, Nat Neurosci, 15, 827, 10.1038/nn.3113 · DOI · Paper page
  54. Leidinger, 2013, A blood based 12-miRNA signature of Alzheimer disease patients, Genome Biol, 14, R78, 10.1186/gb-2013-14-7-r78 · DOI
  55. Lewis, 1993, Insulin-like growth factor-I: potential for treatment of motor neuronal disorders, Exp Neurol, 124, 73, 10.1006/exnr.1993.1177 · DOI
  56. Long, 2013, Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans, BMC Neurol, 13, 178, 10.1186/1471-2377-13-178 · DOI
  57. Mattick, 2004, RNA regulation: a new genetics?, Nat Rev Genet, 5, 316, 10.1038/nrg1321 · DOI · Paper page
  58. Mense, 2000, Neurobiological concepts of fibromyalgia–the possible role of descending spinal tracts, Scand J Rheumatol Suppl, 113, 24, 10.1080/030097400446599 · DOI
  59. Oaklander, 2013, Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia, PAIN, 154, 2310, 10.1016/j.pain.2013.06.001 · DOI · Paper page
  60. Offenbaecher, 2000, Validation of a German version of the fibromyalgia impact questionnaire (FIQ-G), J Rheumatol, 27, 1984
  61. Orlova, 2011, MicroRNA modulation in complex regional pain syndrome, J Transl Med, 9, 195, 10.1186/1479-5876-9-195 · DOI
  62. Ozdinler, 2006, IGF-I specifically enhances axon outgrowth of corticospinal motor neurons, Nat Neurosci, 9, 1371, 10.1038/nn1789 · DOI · Paper page
  63. Paraskevopoulou, 2013, DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows, Nucleic Acids Res, 41, W169, 10.1093/nar/gkt393 · DOI
  64. Pauley, 2008, Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients, Arthritis Res Ther, 10, R101, 10.1186/ar2493 · DOI
  65. Philippou, 2007, The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology, In Vivo, 21, 45
  66. Pierson, 2003, Insulin deficiency rather than hyperglycemia accounts for impaired neurotrophic responses and nerve fiber regeneration in type 1 diabetic neuropathy, J Neuropathol Exp Neurol, 62, 260, 10.1093/jnen/62.3.260 · DOI
  67. Rabinovsky, 2004, The multifunctional role of IGF-1 in peripheral nerve regeneration, Neurol Res, 26, 204, 10.1179/016164104225013851 · DOI
  68. Rolke, 2006, Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values, PAIN, 123, 231, 10.1016/j.pain.2006.01.041 · DOI
  69. Roush, 2008, The let-7 family of microRNAs, Trends Cell Biol, 18, 505, 10.1016/j.tcb.2008.07.007 · DOI
  70. Saperstein, 2013, Usefulness of skin biopsies in the evaluation and management of patients with suspected small fiber neuropathy, Int J Neurosci, 123, 38, 10.3109/00207454.2012.723652 · DOI
  71. Serra, 2014, Hyperexcitable C nociceptors in fibromyalgia, Ann Neurol, 75, 196, 10.1002/ana.24065 · DOI · Paper page
  72. Slaby, 2012, Genetic polymorphisms and microRNAs: new direction in molecular epidemiology of solid cancer, J Cell Mol Med, 16, 8, 10.1111/j.1582-4934.2011.01359.x · DOI
  73. Smith, 2010, Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases?, Pharmacol Rev, 62, 199, 10.1124/pr.109.002469 · DOI
  74. Sommer, 2012, Etiology and pathophysiology of fibromyalgia syndrome [in German], Schmerz, 26, 259, 10.1007/s00482-012-1174-0 · DOI
  75. Sommer, 2011, A modified score to identify and discriminate neuropathic pain: a study on the German version of the Neuropathic Pain Symptom Inventory (NPSI), BMC Neurol, 11, 104, 10.1186/1471-2377-11-104 · DOI
  76. Syroid, 1999, A role for insulin-like growth factor-I in the regulation of Schwann cell survival, J Neurosci, 19, 2059, 10.1523/JNEUROSCI.19-06-02059.1999 · DOI
  77. Tokumaru, 2008, let-7 regulates Dicer expression and constitutes a negative feedback loop, Carcinogenesis, 29, 2073, 10.1093/carcin/bgn187 · DOI
  78. Üçeyler, 2010, Elevated proinflammatory cytokine expression in affected skin in small fiber neuropathy, Neurology, 74, 1806, 10.1212/WNL.0b013e3181e0f7b3 · DOI
  79. Üçeyler, 2014, Skin cytokine expression in patients with fibromyalgia syndrome is not different from controls, BMC Neurol, 14, 185, 10.1186/s12883-014-0185-0 · DOI
  80. Üçeyler, 2006, Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain, Arthritis Rheum, 54, 2656, 10.1002/art.22026 · DOI
  81. Üçeyler, 2013, Small fibre pathology in patients with fibromyalgia syndrome, Brain, 136, 1857, 10.1093/brain/awt053 · DOI · Paper page
  82. Vlachos, 2015, DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions, Nucleic Acids Res, 43, D153, 10.1093/nar/gku1215 · DOI
  83. Vlckova-Moravcova, 2008, Diagnostic validity of epidermal nerve fiber densities in painful sensory neuropathies, Muscle Nerve, 37, 50, 10.1002/mus.20889 · DOI
  84. Von Korff, 1992, Grading the severity of chronic pain, PAIN, 50, 133, 10.1016/0304-3959(92)90154-4 · DOI · Paper page
  85. von Schack, 2011, Dynamic changes in the microRNA expression profile reveal multiple regulatory mechanisms in the spinal nerve ligation model of neuropathic pain, PLoS One, 6, e17670, 10.1371/journal.pone.0017670 · DOI
  86. Wang, 2008, Circulating cytokine levels compared to pain in patients with fibromyalgia—a prospective longitudinal study over 6 months, J Rheumatol, 35, 1366
  87. Wang, 2013, MicroRNA in myogenesis and muscle atrophy, Curr Opin Clin Nutr Metab Care, 16, 258, 10.1097/MCO.0b013e32835f81b9 · DOI
  88. Wolfe, 1990, The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee, Arthritis Rheum, 33, 160, 10.1002/art.1780330203 · DOI · Paper page
  89. Xu, 2001, Altered immediate early gene expression in injured diabetic nerve: implications in regeneration, J Neuropathol Exp Neurol, 60, 972, 10.1093/jnen/60.10.972 · DOI
  90. Xu, 2004, Insulin as an in vivo growth factor, Exp Neurol, 188, 43, 10.1016/j.expneurol.2004.03.008 · DOI
  91. Zhang, 2013, The polymorphism in the let-7 targeted region of the Lin28 gene is associated with increased risk of type 2 diabetes mellitus, Mol Cell Endocrinol, 375, 53, 10.1016/j.mce.2013.04.022 · DOI
  92. Zhao, 2013, MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulin-like growth factor-1 receptor, Oncogene, 32, 1363, 10.1038/onc.2012.156 · DOI

Cited by

Sorted by citations

See all 71

Metadata

Authors
Leinders, M., Doppler, K., Klein, T., Deckart, M., Rittner, H., Sommer, C., & Üçeyler, N.
Affiliations
  • University of Würzburg (DE)
  • Pain Clinic Am Arkauwald, Bad Mergentheim, Germany
Corresponding author
Üçeyler, Nurcan
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-07-15
Volume
157
Issue
11
Pages
2493-2503
ISSN
  • 0304-3959 (ISSN-L)
  • 1872-6623
DOI
10.1097/j.pain.0000000000000668
OpenAlex
W2466067781
Cited by
71
References
1
Citations by year
2026: 4 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 9 · 2019: 10 · 2018: 6 · 2017: 10 · 2016: 1
FWCI
7.99
Type
journal article
Language
en
Open access
closed
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
Funders
Julius-Maximilians-Universität Würzburg
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
fibromyalgia, microRNA expression, intraepidermal nerve fiber density, IGF-1 receptor, leukocytes, chronic widespread pain, neuropathic pain
MeSH terms
Small Fiber Neuropathy, Adult, Aged, Female, Fibromyalgia, Humans, Leukocytes, Male, Middle Aged, Pain Measurement, Surveys and Questionnaires, RNA, Messenger, Severity of Illness Index, Skin, Gene Expression, Pain Threshold, Statistics, Nonparametric, MicroRNAs, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome. https://app.cochat.ai/papers/10.1097/j.pain.0000000000000668
The paper
Leinders, M., Doppler, K., Klein, T., Deckart, M., Rittner, H., Sommer, C., & Üçeyler, N. (2016). Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome. Pain. https://doi.org/10.1097/j.pain.0000000000000668