Characterization of dermal skin innervation in fibromyalgia syndrome
Autoři:
Dimitar Evdokimov aff001; Philine Dinkel aff001; Johanna Frank aff001; Claudia Sommer aff001; Nurcan Üçeyler aff001
Působiště autorů:
Department of Neurology, University of Würzburg, Würzburg, Germany
aff001
Vyšlo v časopise:
PLoS ONE 15(1)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0227674
Souhrn
Introduction
We characterized dermal innervation in patients with fibromyalgia syndrome (FMS) as potential contribution to small fiber pathology.
Methods
Skin biopsies of the calf were collected (86 FMS patients, 35 healthy controls). Skin was immunoreacted with antibodies against protein gene product 9.5, calcitonine gene-related peptide, substance P, CD31, and neurofilament 200 for small fiber subtypes. We assessed two skin sections per patient; on each skin section, two dermal areas (150 x 700 μm each) were investigated for dermal nerve fiber length (DNFL).
Results
In FMS patients we found reduced DNFL of fibers with vessel contact compared to healthy controls (p<0.05). There were no differences for the other nerve fiber subtypes.
Discussion
We found less dermal nerve fibers in contact with blood vessels in FMS patients than in controls. The pathophysiological relevance of this finding is unclear, but we suggest the possibility of a relationship with impaired thermal tolerance commonly reported by FMS patients.
Klíčová slova:
Biopsy – Blood vessels – Epidermis – Fibromyalgia – Immunohistochemistry techniques – Nerve fibers – Myelinated nerve fibers – Nerve conduction study
Zdroje
1. Caro XJ, Winter EF. Evidence of abnormal epidermal nerve fiber density in fibromyalgia: clinical and immunologic implications. Arthritis Rheumatol. 2014;66: 1945–1954. doi: 10.1002/art.38662 24719395
2. Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. 2013;154: 2310–2316. doi: 10.1016/j.pain.2013.06.001 23748113
3. Serra J, Collado A, Sola R, Antonelli F, Torres X, Salgueiro M, et al. Hyperexcitable C nociceptors in fibromyalgia. Ann Neurol. 2014;75: 196–208. doi: 10.1002/ana.24065 24243538
4. Üçeyler N, Zeller D, Kahn AK, Kewenig S, Kittel-Schneider S, Schmid A, et al. Small fibre pathology in patients with fibromyalgia syndrome. Brain. 2013;136: 1857–1867. doi: 10.1093/brain/awt053 23474848
5. Dalsgaard CJ, Rydh M, Haegerstrand A. Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. Histochemistry. 1989;92: 385–390. doi: 10.1007/bf00492495 2531128
6. McCarthy BG, Hsieh ST, Stocks A, Hauer P, Macko C, Cornblath DR, et al. Cutaneous innervation in sensory neuropathies: evaluation by skin biopsy. Neurology. 1995;45: 1848–1855. doi: 10.1212/wnl.45.10.1848 7477980
7. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139: 267–284. doi: 10.1016/j.cell.2009.09.028 19837031
8. Duraku LS, Hossaini M, Schuttenhelm BN, Holstege JC, Baas M, Ruigrok TJ, et al. Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain. Exp Neurol. 2013;241: 13–24. doi: 10.1016/j.expneurol.2012.11.029 23219885
9. Kambiz S, Duraku LS, Baas M, Nijhuis TH, Cosgun SG, Hovius SE, et al. Long-term follow-up of peptidergic and nonpeptidergic reinnervation of the epidermis following sciatic nerve reconstruction in rats. J Neurosurg. 2015;123: 254–269. doi: 10.3171/2014.12.JNS141075 25723305
10. Lindenlaub T, Sommer C. Epidermal innervation density after partial sciatic nerve lesion and pain-related behavior in the rat. Acta Neuropathologica. 2002;104: 137–143. doi: 10.1007/s00401-002-0527-7 12111356
11. Evdokimov D, Frank J, Klitsch A, Unterecker S, Warrings B, Serra J, et al. Reduction of skin innervation is associated with a severe fibromyalgia phenotype. Ann Neurol. 2019;86: 504–516. doi: 10.1002/ana.25565 31376174
12. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010;62: 600–610.
13. Eich W, Hauser W, Arnold B, Jackel W, Offenbacher M, Petzke F, et al. [Fibromyalgia syndrome. Definition, classification, clinical diagnosis and prognosis]. Schmerz. 2012;26: 247–258. doi: 10.1007/s00482-012-1169-x 22760457
14. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33: 160–172. doi: 10.1002/art.1780330203 2306288
15. Kimura J. Electrodiagnosis in diseases of nerve and muscle: Principles and practice. New York: Oxford University Press. Third edition. 2001;
16. Üçeyler N, Kafke W, Riediger N, He L, Necula G, Toyka KV, et al. Elevated proinflammatory cytokine expression in affected skin in small fiber neuropathy. Neurology. 2010;74: 1806–1813. doi: 10.1212/WNL.0b013e3181e0f7b3 20513817
17. Lauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI, Nolano M, et al. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol. 2005;12: 747–758. doi: 10.1111/j.1468-1331.2005.01260.x 16190912
18. Lauria G, Cazzato D, Porretta-Serapiglia C, Casanova-Molla J, Taiana M, Penza P, et al. Morphometry of dermal nerve fibers in human skin. Neurology. 2011;77: 242–249. doi: 10.1212/WNL.0b013e318225ab51 21734180
19. Müller AM, Hermanns MI, Skrzynski C, Nesslinger M, Müller KM, Kirkpatrick CJ. Expression of the endothelial markers PECAM-1, vWf, and CD34 in vivo and in vitro. Exp Mol Pathol. 2002;72: 221–229. doi: 10.1006/exmp.2002.2424 12009786
20. Schulze E, Witt M, Fink T, Hofer A, Funk RH. Immunohistochemical detection of human skin nerve fibers. Acta Histochem. 1997;99: 301–309. doi: 10.1016/S0065-1281(97)80024-4 9381913
21. Dalsgaard CJ, Jonsson CE, Hokfelt T, Cuello AC. Localization of substance P-immunoreactive nerve fibers in the human digital skin. Experientia. 1983;39: 1018–1020. doi: 10.1007/bf01989781 6193004
22. Wallengren J, Sundler F. Phototherapy reduces the number of epidermal and CGRP-positive dermal nerve fibres. Acta Derm Venereol. 2004;84: 111–115. doi: 10.1080/00015550310022899 15206689
23. Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998;18: 8947–8959. doi: 10.1523/JNEUROSCI.18-21-08947.1998 9787000
24. Karlsson P, Porretta-Serapiglia C, Lombardi R, Jensen TS, Lauria G. Dermal innervation in healthy subjects and small fiber neuropathy patients: a stereological reappraisal. J Peripher Nerv Syst. 2013;18: 48–53. doi: 10.1111/jns5.12007 23521644
25. Albrecht PJ, Hou Q, Argoff CE, Storey JR, Wymer JP, Rice FL. Excessive peptidergic sensory innervation of cutaneous arteriole-venule shunts (AVS) in the palmar glabrous skin of fibromyalgia patients: implications for widespread deep tissue pain and fatigue. Pain Med. 2013;14: 895–915. doi: 10.1111/pme.12139 23691965
26. Morf S, Amann-Vesti B, Forster A, Franzeck UK, Koppensteiner R, Uebelhart D, et al. Microcirculation abnormalities in patients with fibromyalgia—measured by capillary microscopy and laser fluxmetry. Arthritis Res Ther. 2005;7: R209–R216. doi: 10.1186/ar1459 15743467
27. Zamuner AR, Barbic F, Dipaola F, Bulgheroni M, Diana A, Atzeni F, et al. Relationship between sympathetic activity and pain intensity in fibromyalgia. Clin Exp Rheumatol. 2015;33: S53–57. 25786044
28. Bennett RM, Clark SR, Campbell SM, Ingram SB, Burckhardt CS, Nelson DL, et al. Symptoms of Raynaud's syndrome in patients with fibromyalgia. A study utilizing the Nielsen test, digital photoplethysmography, and measurements of platelet alpha 2-adrenergic receptors. Arthritis Rheum. 1991;34: 264–269. doi: 10.1002/art.1780340303 1848429
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