Skip to main content
SpringerLink
Log in

The Neuroscience of Fibromyalgia and Central Sensitization

  • Chapter
  • First Online:
Fibromyalgia Syndrome

Abstract

Central sensitization was first described in the 1980s as a spinal mechanism of augmenting painful stimuli, causing hyperalgesia and allodynia. During the years to follow it was discovered that parts of the brain are also involved in this inadequate amplification of sensory inputs.

It is believed that chronic pain syndromes, including fibromyalgia, irritable bowel syndrome, endometriosis, etc., all share common features of central sensitization, and were therefore gathered under the definition of chronic overlapping pain conditions (COPC). However, central sensitization may also be secondary to other conditions, such as malignancy and autoimmune diseases, causing patients to suffer from fibromyalgia-like symptoms.

Central sensitization is thought to arise from both genetic and environmental triggers: Long-standing acute pain and psychosocial stress are suggested as major contributing factors to COPCs, but although some genetic predispositions were described, they have not yet been fully defined.

From a neurophysiologic perspective, it is known that chronic pain syndromes are associated with altered conditioned pain modulation (CPM), the body’s mechanism of suppressing painful stimuli. Neuroimaging studies in these patients show structural changes in different body areas, with alterations in neurotransmitter concentrations, both excitatory and inhibitory.

Our understanding of the pathophysiology of central sensitization is rapidly evolving, and current works also focus on immunologic alterations involved in the process, such as elevated interleukin levels and chronic inflammatory processes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature. 1983 Dec 15–21;306(5944):686–8.

    Google Scholar 

  2. Sluka KA, Westlund KN. An experimental arthritis in rats: dorsal horn aspartate and glutamate increases. Neurosci Lett. 1992 Oct 12;145(2):141–144. Epub 1992/10/12. English.

    Google Scholar 

  3. Dougherty PM, Palecek J, Paleckova V, Sorkin LS, Willis WD. The role of NMDA and non-NMDA excitatory amino acid receptors in the excitation of primate spinothalamic tract neurons by mechanical, chemical, thermal, and electrical stimuli. J Neurosci. 1992 Aug;12(8):3025–3041. Epub 1992/08/01.

    Google Scholar 

  4. Willis WD, Jr. Dorsal horn neurophysiology of pain. Ann N Y Acad Sci. 1988;531:76–89. Epub 1988/01/01.

    Google Scholar 

  5. Treede RD, Davis KD, Campbell JN, Raja SN. The plasticity of cutaneous hyperalgesia during sympathetic ganglion blockade in patients with neuropathic pain. Brain. 1992 Apr;115 (Pt 2):607–621. Epub 1992/04/01.

    Google Scholar 

  6. Willis WD, Jr. Central nervous system mechanisms for pain modulation. Appl Neurophysiol. 1985;48(1–6):153–165. Epub 1985/01/01.

    Google Scholar 

  7. Yaksh TL. CNS mechanisms of pain and analgesia. Cancer Surv. 1988;7(1):5–28. Epub 1988/01/01.

    Google Scholar 

  8. Sorensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M. Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol. 1995;24(6):360–365. Epub 1995/01/01.

    Google Scholar 

  9. Gibson SJ, Littlejohn GO, Gorman MM, Helme RD, Granges G. Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome. Pain. 1994 Aug;58(2):185–193. Epub 1994/08/01.

    Google Scholar 

  10. Granges G, Littlejohn G. Pressure pain threshold in pain-free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome. Arthritis Rheum. 1993 May;36(5):642–646. Epub 1993/05/01.

    Google Scholar 

  11. Mertz H, Naliboff B, Munakata J, Niazi N, Mayer EA. Altered rectal perception is a biological marker of patients with irritable-bowel-syndrome. Gastroenterology. 1995 Jul;109(1):40–52. PubMed PMID: WOS:A1995RG19100005. English.

    Google Scholar 

  12. Gracely RH, Lynch SA, Bennett GJ. Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain. 1992 Nov;51(2):175–194. Epub 1992/11/01.

    Google Scholar 

  13. Siao P, Cros DP. Quantitative sensory testing. Phys Med Rehabil Clin N Am. 2003 May;14(2):261–86.

    Article  Google Scholar 

  14. Levitt AE, Galor A, Chowdhury AR, Felix ER, Sarantopoulos CD, Zhuang GY, et al. Evidence that dry eye represents a chronic overlapping pain condition. Mol Pain. 2017 Jan–Dec;13:1744806917729306. Pubmed Central PMCID: PMC5584655. Epub 2017/08/18.

    Google Scholar 

  15. Maixner W, Fillingim RB, Williams DA, Smith SB, Slade GD. Overlapping chronic pain conditions: implications for diagnosis and classification. J Pain. 2016 Sep;17(9 Suppl):T93–T107. Epub 2016/09/03. eng.

    Google Scholar 

  16. Gwilym SE, Filippini N, Douaud G, Carr AJ, Tracey I. Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: a longitudinal voxel-based morphometric study. Arthritis Rheum. 2010 Oct;62(10):2930–2940. Epub 2010/06/03. eng.

    Google Scholar 

  17. Kosek E, Ordeberg G. Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following, surgical pain relief. Pain. 2000;88(1):69–78.

    Article  Google Scholar 

  18. Staud R, Weyl EE, Bartley E, Price DD, Robinson ME. Analgesic and anti-hyperalgesic effects of muscle injections with lidocaine or saline in patients with fibromyalgia syndrome. Eur J Pain. 2014 Jul;18(6):803–812. Pubmed Central PMCID: PMC4010579. Epub 2013/11/07.

    Google Scholar 

  19. Warren JW, Howard FM, Cross RK, Good JL, Weissman MM, Wesselmann U, et al. Antecedent nonbladder syndromes in case-control study of interstitial cystitis/painful bladder syndrome. Urology. 2009 Jan;73(1):52–57. Epub 2008/11/11.

    Google Scholar 

  20. Williams DA, Clauw DJ. Understanding fibromyalgia: lessons from the broader pain research community. J Pain. 2009 Aug;10(8):777–791. Pubmed Central PMCID: PMC2741022. Epub 2009/07/30. eng.

    Google Scholar 

  21. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;152(3 Suppl):S2–15. Pubmed Central PMCID: PMC3268359. Epub 2010/10/22. Eng.

    Google Scholar 

  22. Fukuda K, Dobbins JG, Wilson LJ, Dunn RA, Wilcox K, Smallwood D. An epidemiologic study of fatigue with relevance for the chronic fatigue syndrome. J Psychiatr Res. 1997 Jan–Feb;31(1):19–29. Epub 1997/01/01.

    Google Scholar 

  23. Fukuda K, Nisenbaum R, Stewart G, Thompson WW, Robin L, Washko RM, et al. Chronic multisymptom illness affecting Air Force veterans of the Gulf War. JAMA. 1998 Sep 16;280(11):981–988. Epub 1998/09/28.

    Google Scholar 

  24. Kato K, Sullivan PF, Evengard B, Pedersen NL. A population-based twin study of functional somatic syndromes. Psychol Med. 2009 Mar;39(3):497–505. Pubmed Central PMCID: PMC3947533. Epub 2008/06/27. eng.

    Google Scholar 

  25. McLean SA, Diatchenko L, Lee YM, Swor RA, Domeier RM, Jones JS, et al. Catechol O-methyltransferase haplotype predicts immediate musculoskeletal neck pain and psychological symptoms after motor vehicle collision. J Pain. 2011 Jan;12(1):101–107. Pubmed Central PMCID: PMC2975044. Epub 2010/08/07. eng.

    Google Scholar 

  26. Buskila D, Atzeni F, Sarzi-Puttini P. Etiology of fibromyalgia: the possible role of infection and vaccination. Autoimmun Rev. 2008 Oct;8(1):41–43. Epub 2008/08/19.

    Google Scholar 

  27. Clauw DJ. Fibromyalgia: more than just a musculoskeletal disease. Am Fam Physician. 1995 Sep 1;52(3):843–851, 53–4. Epub 1995/09/01. eng.

    Google Scholar 

  28. Epstein SA, Kay G, Clauw D, Heaton R, Klein D, Krupp L, et al. Psychiatric disorders in patients with fibromyalgia. A multicenter investigation. Psychosomatics. 1999 Jan–Feb;40(1):57–63. Epub 1999/02/16.

    Google Scholar 

  29. Diatchenko L, Fillingim RB, Smith SB, Maixner W. The phenotypic and genetic signatures of common musculoskeletal pain conditions. Nat Rev Rheumatol. 2013 Jun;9(6):340–350. Pubmed Central PMCID: PMC3991785. Epub 2013/04/03.

    Google Scholar 

  30. Buskila D, Sarzi-Puttini P, Ablin JN. The genetics of fibromyalgia syndrome. Pharmacogenomics. 2007 Jan;8(1):67–74. Epub 2006/12/26.

    Google Scholar 

  31. Ciampi de Andrade D, Maschietto M, Galhardoni R, Gouveia G, Chile T, Victorino Krepischi AC, et al. Epigenetics insights into chronic pain: DNA hypomethylation in fibromyalgia-a controlled pilot-study. Pain. 2017 Aug;158(8):1473–1480. Epub 2017/06/18.

    Google Scholar 

  32. McDermid AJ, Rollman GB, McCain GA. Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification. Pain. 1996 Aug;66(2–3):133–144. Epub 1996/08/01.

    Google Scholar 

  33. Dohrenbusch R, Sodhi H, Lamprecht J, Genth E. Fibromyalgia as a disorder of perceptual organization? An analysis of acoustic stimulus processing in patients with widespread pain. Z Rheumatol. 1997 Dec;56(6):334–341. Epub 1998/03/06.

    Google Scholar 

  34. Geisser ME, Glass JM, Rajcevska LD, Clauw DJ, Williams DA, Kileny PR, et al. A psychophysical study of auditory and pressure sensitivity in patients with fibromyalgia and healthy controls. J Pain. 2008 May;9(5):417–422. Epub 2008/02/19.

    Google Scholar 

  35. Schweinhardt P, Sauro KM, Bushnell MC. Fibromyalgia: a disorder of the brain? Neurosci Rev J Bring Neurobiol Neurol Psychiatry. 2008 Oct;14(5):415–421. Epub 2008/02/14. eng.

    Google Scholar 

  36. Martenson ME, Halawa OI, Tonsfeldt KJ, Maxwell CA, Hammack N, Mist SD, et al. A possible neural mechanism for photosensitivity in chronic pain. Pain. 2016 Apr;157(4):868–878. Pubmed Central PMCID: PMC4794405. Epub 2016/01/20. Eng.

    Google Scholar 

  37. Diatchenko L, Nackley AG, Slade GD, Bhalang K, Belfer I, Max MB, et al. Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain. 2006 Dec 5;125(3):216–224. Epub 2006/07/14.

    Google Scholar 

  38. Gwilym SE, Keltner JR, Warnaby CE, Carr AJ, Chizh B, Chessell I, et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 2009 Sep 15;61(9):1226–1234. Epub 2009/08/29.

    Google Scholar 

  39. Tracey I, Bushnell MC. How neuroimaging studies have challenged us to rethink: is chronic pain a disease? J Pain. 2009;10(11):1113–20.

    Article  Google Scholar 

  40. Nielsen CS, Staud R, Price DD. Individual differences in pain sensitivity: measurement, causation, and consequences. J Pain. 2009 Mar;10(3):231–237. Epub 2009/02/03. eng.

    Google Scholar 

  41. Neddermeyer TJ, Fluhr K, Lotsch J. Principle components analysis of pain thresholds to thermal, electrical, and mechanical stimuli suggests a predominant common source of variance. Pain. 2008 Aug 31;138(2):286–291. Epub 2008/02/05. eng.

    Google Scholar 

  42. Fillingim RB. Individual differences in pain responses. Curr Rheumatol Rep. 2005 Oct;7(5):342–347. Epub 2005/09/22. eng.

    Google Scholar 

  43. Kleinbohl D, Holzl R, Moltner A, Rommel C, Weber C, Osswald PM. Psychophysical measures of sensitization to tonic heat discriminate chronic pain patients. Pain. 1999 May;81(1–2):35–43. Epub 1999/06/03.

    Google Scholar 

  44. Ablin K, Clauw DJ. From fibrositis to functional somatic syndromes to a bell-shaped curve of pain and sensory sensitivity: evolution of a clinical construct. Rheum Dis Clin N Am. 2009 May;35(2):233–251. Epub 2009/08/04.

    Google Scholar 

  45. Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain. 2012 Oct;13(10):936–944. Epub 2012/09/18.

    Google Scholar 

  46. Youssef AM, Macefield VG, Henderson LA. Cortical influences on brainstem circuitry responsible for conditioned pain modulation in humans. Hum Brain Mapp. 2016 Jul;37(7):2630–2644. Epub 2016/04/23. eng.

    Google Scholar 

  47. Bogdanov VB, Vigano A, Noirhomme Q, Bogdanova OV, Guy N, Laureys S, et al. Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects. Behav Brain Res. 2015 Mar 15;281:187–198. Pubmed Central PMCID: PMC5502003. Epub 2014/12/03. eng.

    Google Scholar 

  48. Sprenger C, Bingel U, Buchel C. Treating pain with pain: supraspinal mechanisms of endogenous analgesia elicited by heterotopic noxious conditioning stimulation. Pain. 2011 Feb;152(2):428–439. Epub 2011/01/05. eng.

    Google Scholar 

  49. Piche M, Arsenault M, Rainville P. Cerebral and cerebrospinal processes underlying counterirritation analgesia. J Neurosci. 2009 Nov 11;29(45):14236–14246. Epub 2009/11/13. eng.

    Google Scholar 

  50. Maixner W, Fillingim R, Sigurdsson A, Kincaid S, Silva S. Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain: evidence for altered temporal summation of pain. Pain. 1998 May;76(1–2):71–81. Epub 1998/08/08.

    Google Scholar 

  51. Sarlani E, Grace EG, Reynolds MA, Greenspan JD. Evidence for up-regulated central nociceptive processing in patients with masticatory myofascial pain. J Orofac Pain. 2004 Winter;18(1):41–55. Epub 2004/03/20.

    Google Scholar 

  52. Weissman-Fogel I, Granovsky Y, Crispel Y, Ben-Nun A, Best LA, Yarnitsky D, et al. Enhanced presurgical pain temporal summation response predicts post-thoracotomy pain intensity during the acute postoperative phase. J Pain. 2009 Jun;10(6):628–636. Epub 2009/04/29.

    Google Scholar 

  53. Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, et al. Sensitization in patients with painful knee osteoarthritis. Pain. 2010 Jun;149(3):573–581. Epub 2010/04/27.

    Google Scholar 

  54. Staud R, Craggs JG, Perlstein WM, Robinson ME, Price DD. Brain activity associated with slow temporal summation of C-fiber evoked pain in fibromyalgia patients and healthy controls. Eur J Pain. 2008 Nov;12(8):1078–1089. Pubmed Central PMCID: PMC2582560. Epub 2008/03/28.

    Google Scholar 

  55. Smallwood RF, Laird AR, Ramage AE, Parkinson AL, Lewis J, Clauw DJ, et al. Structural brain anomalies and chronic pain: a quantitative meta-analysis of gray matter volume. J Pain. 2013 Jul;14(7):663–675. Pubmed Central PMCID: PMC4827858. Epub 2013/05/21.

    Google Scholar 

  56. Harris RE, Clauw DJ. Imaging central neurochemical alterations in chronic pain with proton magnetic resonance spectroscopy. Neurosci Lett. 2012 Jun 29;520(2):192–196. Epub 2012/03/27.

    Google Scholar 

  57. Harte SE, Ichesco E, Hampson JP, Peltier SJ, Schmidt-Wilcke T, Clauw DJ, et al. Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula. Pain. 2016 Sep;157(9):1933–1945. Pubmed Central PMCID: PMC4988086. Epub 2016/04/22.

    Google Scholar 

  58. Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH. Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol. 2004 Feb;31(2):364–378. Epub 2004/02/05. eng.

    Google Scholar 

  59. Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, et al. Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci. 2007 Jun;25(12):3576–3582. Epub 2007/07/06. English.

    Google Scholar 

  60. Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007 Sep 12;27(37):10000–10006. Epub 2007/09/15.

    Google Scholar 

  61. Schrepf A, Harper DE, Harte SE, Wang H, Ichesco E, Hampson JP, et al. Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study. Pain. 2016 Oct;157(10):2217–2225. Pubmed Central PMCID: PMC5028286. Epub 2016/07/16.

    Google Scholar 

  62. Pyke TL, Osmotherly PG, Baines S. Measuring glutamate levels in the brains of fibromyalgia patients and a potential role for glutamate in the pathophysiology of fibromyalgia symptoms: a systematic review. Clin J Pain. 2017 Oct;33(10):944–954. Epub 2016/12/30. eng.

    Google Scholar 

  63. Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance P-facilitated K(+)-evoked release of [(3)H]glutamate from rat caudial trigeminal nucleus slices. Pain. 2001 Aug;93(2):191–196. Epub 2001/06/28.

    Google Scholar 

  64. Chastain G. Alcohol, neurotransmitter systems, and behavior. J Gen Psychol. 2006 Oct;133(4):329–335. Epub 2006/11/30. eng.

    Google Scholar 

  65. Chandler CM, Overton JS, Ruedi-Bettschen D, Platt DM. GABAA receptor subtype mechanisms and the abuse-related effects of ethanol: genetic and pharmacological evidence. Handb Exp Pharmacol. 2017 Dec 5. Epub 2017/12/06. eng.

    Google Scholar 

  66. Gur A, Oktayoglu P. Status of immune mediators in fibromyalgia. Curr Pain Headache Rep. 2008 Jun;12(3):175–181. Epub 2008/09/18.

    Google Scholar 

  67. Bazzichi L, Rossi A, Massimetti G, Giannaccini G, Giuliano T, De Feo F, et al. Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clin Exp Rheumatol. 2007 Mar–Apr;25(2):225–30. PubMed PMID: WOS:000246882200214. English.

    Google Scholar 

  68. Schrepf A, Harte SE, Miller N, Fowler C, Nay C, Williams DA, et al. Improvement in the spatial distribution of pain, somatic symptoms, and depression after a weight loss intervention. J Pain. 2017 Dec;18(12):1542–1550. Pubmed Central PMCID: PMC5841588. Epub 2017/08/30.

    Google Scholar 

  69. Wolfe F. Fibromyalgianess. Arthritis Rheum. 2009 Jun 15;61(6):715–716. Epub 2009/05/30. eng.

    Google Scholar 

  70. 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 May;62(5):600–610. Epub 2010/05/13.

    Google Scholar 

  71. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Hauser W, Katz RS, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol. 2011 Jun;38(6):1113–1122. Epub 2011/02/03. Eng.

    Google Scholar 

  72. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Hauser W, Katz RL, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016 Dec;46(3):319–329. Epub 2016/12/06. eng.

    Google Scholar 

  73. Wolfe F, Michaud K, Busch RE, Katz RS, Rasker JJ, Shahouri SH, et al. Polysymptomatic distress in patients with rheumatoid arthritis: understanding disproportionate response and its spectrum. Arthritis Care Res (Hoboken). 2014 Oct;66(10):1465–1471. Epub 2014/02/06.

    Google Scholar 

  74. Wolfe F, Michaud K, Li T, Katz RS. Chronic conditions and health problems in rheumatic diseases: comparisons with rheumatoid arthritis, noninflammatory rheumatic disorders, systemic lupus erythematosus, and fibromyalgia. J Rheumatol. 2010 Feb;37(2):305–315. Epub 2010/01/19. eng.

    Google Scholar 

  75. Brummett CM, Bakshi RR, Goesling J, Leung D, Moser SE, Zollars JW, et al. Preliminary validation of the Michigan Body Map. Pain. 2016 Jun;157(6):1205–1212. Pubmed Central PMCID: PMC4868633. Epub 2016/02/03.

    Google Scholar 

  76. Brummett CM, Janda AM, Schueller CM, Tsodikov A, Morris M, Williams DA, et al. Survey criteria for fibromyalgia independently predict increased postoperative opioid consumption after lower-extremity joint arthroplasty: a prospective, observational cohort study. Anesthesiology. 2013 Dec;119(6):1434–1443. Pubmed Central PMCID: PMC3867739. Epub 2013/12/18. eng.

    Google Scholar 

  77. Brummett CM, Urquhart AG, Hassett AL, Tsodikov A, Hallstrom BR, Wood NI, et al. Characteristics of fibromyalgia independently predict poorer long-term analgesic outcomes following total knee and hip arthroplasty. Arthritis Rheumatol. 2015 May;67(5):1386–1394. Pubmed Central PMCID: PMC4414825. Epub 2015/03/17.

    Google Scholar 

  78. Janda AM, As-Sanie S, Rajala B, Tsodikov A, Moser SE, Clauw DJ, et al. Fibromyalgia survey criteria are associated with increased postoperative opioid consumption in women undergoing hysterectomy. Anesthesiology. 2015 May;122(5):1103–1111. Epub 2015/03/15.

    Google Scholar 

  79. Kim SH, Kim DH, Oh DH, Clauw DJ. Characteristic electron microscopic findings in the skin of patients with fibromyalgia: preliminary study. Clin Rheumatol. 2008 Feb;27(2):219–223. Epub 2007/10/04.

    Google Scholar 

  80. Doppler K, Rittner HL, Deckart M, Sommer C. Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia. Pain. 2015 Nov;156(11):2319–2325. Epub 2015/07/15.

    Google Scholar 

  81. Levine TD, Saperstein DS. Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients. Clin Rheumatol. 2015 Mar;34(3):413–417. Pubmed Central PMCID: PMC4348533. Epub 2014/12/24. Eng.

    Google Scholar 

  82. Caro XJ, Winter EF. The role and importance of small fiber neuropathy in fibromyalgia pain. Curr Pain Headache Rep. 2015 Dec;19(12):55. Epub 2015/10/27. Eng.

    Google Scholar 

  83. Uceyler N, Zeller D, Kahn AK, Kewenig S, Kittel-Schneider S, Schmid A, et al. Small fibre pathology in patients with fibromyalgia syndrome. Brain. 2013 Jun;136(Pt 6):1857–1867. Epub 2013/03/12. Eng.

    Google Scholar 

  84. Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. 2013 Nov;154(11):2310–2316. Pubmed Central PMCID: PMC3845002. Epub 2013/06/12. Eng.

    Google Scholar 

  85. Clauw DJ. What is the meaning of “small fiber neuropathy” in fibromyalgia? Pain. 2015 Aug 19.

    Google Scholar 

  86. Harte SE, Clauw DJ, Hayes JM, Feldman EL, St Charles IC, Watson CJ. Reduced intraepidermal nerve fiber density after a sustained increase in insular glutamate: a proof-of-concept study examining the pathogenesis of small fiber pathology in fibromyalgia. Pain Rep. 2017 May;2(3):e590. Pubmed Central PMCID: PMC5741296. Epub 2018/02/03.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Michigan, Chronic Pain and Fatigue Research Center, Ann Arbor, MI, USA

    Daniel J. Clauw

  2. Internal Medicine H, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Roie Tzadok

Authors
  1. Daniel J. Clauw
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roie Tzadok
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roie Tzadok .

Editor information

Editors and Affiliations

  1. Tel Aviv Sourasky Medical Center & Tel Aviv University School of Medicine, Tel Aviv, Israel

    Jacob N. Ablin

  2. Ariel University, Ariel, Israel

    Yehuda Shoenfeld

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Clauw, D.J., Tzadok, R. (2021). The Neuroscience of Fibromyalgia and Central Sensitization. In: Ablin, J.N., Shoenfeld, Y. (eds) Fibromyalgia Syndrome . Springer, Cham. https://doi.org/10.1007/978-3-030-78638-0_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-78638-0_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-78637-3

  • Online ISBN: 978-3-030-78638-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation