International Urogynecology Journal

, Volume 30, Issue 11, pp 1817–1820 | Cite as

Small fiber polyneuropathy as a potential therapeutic target in interstitial cystitis/bladder pain syndrome

  • Catherine A. Matthews
  • Shaun P. Deveshwar
  • Robert J. Evans
  • Gopal Badlani
  • Stephen J. WalkerEmail author
Review Article


Introduction and hypothesis

Interstitial cystitis/bladder pain syndrome (IC/BPS) and fibromyalgia (FM) are frequently co-occurring medical diagnoses in patients referred to the urology clinic for secondary and tertiary treatment options.


Abundant literature has shown that many patients with FM have small fiber polyneuropathy (SFPN) that can be confirmed via skin punch biopsy and immunological staining to measure nerve density.

Results and conclusions

This finding of SFPN provides a therapeutic target for FM and in this article we hypothesize and provide rationale for the idea that this same phenomenon (SFPN) might explain, in some IC/BPS patients, the finding of widespread pain and likewise provide a therapeutic target for these patients.


Polyneuropathy Interstitial cystitis/bladder pain syndrome Fibromyalgia 



This study was funded by NIH/NIDDK Grant 5R21DK106554-02 (SJW).

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Caro XJ, Winter EF, Dumas A. A subset of fibromyalgia patients have findings suggestive of chronic inflammatory demyelinating polyneuropathy (CIDP) and appear to respond to IVIG. Rheumatology (Oxford). 2008;47:208–11.CrossRefGoogle Scholar
  2. 2.
    Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. 2013;154:2310–6.CrossRefGoogle Scholar
  3. 3.
    Clauw DJ, Schmidt M, Radulovic D, Singer A, Katz P, Bresette J. The relationship between fibromyalgia and interstitial cystitis. J Psychiatr Res. 1997;31:125–31.CrossRefGoogle Scholar
  4. 4.
    Chelimsky G, Heller E, Buffington CA, Rackley R, Zhang D, Chelimsky T. Co-morbidities of interstitial cystitis. Front Neurosci. 2012;6:1–6.CrossRefGoogle Scholar
  5. 5.
    Walker SJ, Zambon J, Andersson KE, Langefeld CD, Matthews CA, Badlani G, et al. Bladder capacity is a biomarker for a bladder centric versus systemic manifestation in interstitial cystitis/bladder pain syndrome. J Urol. 2017;198:369–75.CrossRefGoogle Scholar
  6. 6.
    Lai HH, Jemielita T, Sutcliffe S, Bradley CS, Naliboff B, Williams DA, et al. Characterization of whole body pain in urologic chronic pelvic pain syndrome at baseline—a MAPP research network study. J Urol. 2017;198:622–31.CrossRefGoogle Scholar
  7. 7.
    Oaklander AL. What is the meaning of "small-fiber polyneuropathy" in fibromyalgia? An alternate answer. Pain. 2016;157:1366–7.CrossRefGoogle Scholar
  8. 8.
    Levine TD. Small fiber neuropathy: disease classification beyond pain and burning. J Cent Nerv Syst Dis. 2018;10:11795735518771703.CrossRefGoogle Scholar
  9. 9.
    Chen A, De E, Agroff C. Small fiber polyneuropathy is prevalent in patients experiencing complex chronic pelvic pain. Pain Med. 2018;20:521–7.CrossRefGoogle Scholar
  10. 10.
    Levine TD, Saperstein DS. Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients. Clin Rheumatol. 2015;34:413–7.CrossRefGoogle Scholar
  11. 11.
    Caro XJ, Winter EF. Evidence of abnormal epidermal nerve fiber density in fibromyalgia: clinical and immunologic implications. Arthritis Rheumatol. 2014;66:1945–54.CrossRefGoogle Scholar
  12. 12.
    Grayston R, Czanner G, Elhadd K, Goebel A, Frank B, Uceyler N, et al. A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: implications for a new paradigm in fibromyalgia etiopathogenesis. Semin Arthritis Rheum. 2019;48:933–40.CrossRefGoogle Scholar
  13. 13.
    Christmas TJ, Rode J, Chapple CR, Milroy EJG, Turner-Warwick RT. Nerve fibre proliferation in interstitial cystitis. Virchows Arch A Pathol Anat Histopathol. 1990;416:447–51.CrossRefGoogle Scholar
  14. 14.
    Oaklander AL. Immunotherapy prospects for painful small-fiber sensory neuropathies and ganglionopathies. Neurotherapeutics. 2016;13:108–17.CrossRefGoogle Scholar
  15. 15.
    Caro XJ, Winter EF. The role and importance of small fiber neuropathy in fibromyalgia pain. Curr Pain Headache Rep. 2015;19:55.CrossRefGoogle Scholar
  16. 16.
    Mullins C, Bavendam T, Kirkali Z, Kusek JW. Novel research approaches for interstitial cystitis/bladder pain syndrome: thinking beyond the bladder. Transl Androl Urol. 2015;4(5):524–33.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, et al. Interstitial cystitis guidelines panel of the American urological association education and research, Inc. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011;185:2162–70.CrossRefGoogle Scholar

Copyright information

© The International Urogynecological Association 2019

Authors and Affiliations

  1. 1.Department of Urology/Female Pelvic HealthWake Forest Baptist Medical CenterWinston-SalemUSA
  2. 2.Wake Forest Institute for Regenerative MedicineWake Forest Baptist Medical CenterWinston SalemUSA

Personalised recommendations