Pruritus pp 57-65 | Cite as

Measurement of Sensory Function in Chronic Pruritus

  • Esther Pogatzki-ZahnEmail author
  • Manuel P. Pereira
  • Martin Tegenthoff


Chronic pruritus may be caused by dysfunction in cutaneous receptors, arise from peripheral nerve damage or have its genesis in the central nervous system. In combination with a detailed clinical history, neurophysiological examinations allow physicians to objectively confirm a lesion in the somatosensory system and detect its origin. Moreover, the assessment of the sensory function is important to achieve a precise characterization of the sensory dysfunction and to monitor the response to treatment. Nerve conduction studies and somatosensory evoked potentials are routinely used in the examination of large myelinated fibers, whereas quantitative sensory testing is used to evaluate the function of small myelinated and unmyelinated peripheral nerve fibers. The quantification of intraepidermal nerve fiber density, by analysis of skin biopsies, or assessments of corneal nerves by corneal confocal microscopy allow the study of morphological changes. These structural diagnostic tools do not assess sensory function directly, but are valuable in predicting sensory dysfunction. A combination of neurophysiological examinations is often necessary to obtain a comprehensive sensory profile of the individual patient and thus better guide therapy. Other specialized methodologies as microneurography and nociceptive evoked potentials have yet limited clinical application and are mainly used for research purposes. Aim of this chapter is to give an overview of neurophysiological examinations used to assess sensory function and to briefly discuss their role in the assessment of chronic itch. Three clinical cases are presented at the end of this chapter to illustrate the practical application of these examinations.


Chronic pruritus Corneal confocal microscopy Intraepidermal nerve fiber density Microneurography Nerve conduction studies Neurophysiology Nociceptive evoked potentials Quantitative sensory testing Sensory function Small fiber neuropathy Somatosensory evoked potentials Somatosensory system 


  1. 1.
    Twycross R, Greaves MW, Handwerker H, Jones EA, Libretto SE, Szepietowski JC, Zylicz Z. Itch: scratching more than the surface. QJM. 2003;96(1):7–26.CrossRefPubMedGoogle Scholar
  2. 2.
    Stander S, Schmelz M. Chronic itch and pain – similarities and differences. Eur J Pain. 2006;10(5):473–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Stander S. Chronic pruritus: principals of diagnostics and therapy. Hautarzt. 2007;58(7):627–36.CrossRefPubMedGoogle Scholar
  4. 4.
    Garcia-Larrea L. Objective pain diagnostics: clinical neurophysiology. Neurophysiol Clin. 2012;42(4):187–97.CrossRefPubMedGoogle Scholar
  5. 5.
    Backonja MM, Attal N, Baron R, Bouhassira D, Drangholt M, Dyck PJ, Edwards RR, Freeman R, Gracely R, Haanpaa MH, Hansson P, Hatem SM, Krumova EK, Jensen TS, Maier C, Mick G, Rice AS, Rolke R, Treede RD, Serra J, Toelle T, Tugnoli V, Walk D, Walalce MS, Ware M, Yarnitsky D, Ziegler D. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain. 2013;154(9):1807–19.CrossRefPubMedGoogle Scholar
  6. 6.
    Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sole J. 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. Eur J Neurol. 2010;17(7):903–12, e44–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Mallik A, Weir AI. Nerve conduction studies: essentials and pitfalls in practice. J Neurol Neurosurg Psychiatry. 2005;76 Suppl 2:ii23–31.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Cohen AD, Masalha R, Medvedovsky E, Vardy DA. Brachioradial pruritus: a symptom of neuropathy. J Am Acad Dermatol. 2003;48(6):825–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Cohen AD, Vander T, Medvendovsky E, Biton A, Naimer S, Shalev R, Vardy DA. Neuropathic scrotal pruritus: anogenital pruritus is a symptom of lumbosacral radiculopathy. J Am Acad Dermatol. 2005;52(1):61–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Solak O, Kulac M, Yaman M, Karaca S, Toktas H, Kirpiko O, Kavuncu V. Lichen simplex chronicus as a symptom of neuropathy. Clin Exp Dermatol. 2009;34(4):476–80.CrossRefPubMedGoogle Scholar
  11. 11.
    Cohen AD, Andrews ID, Medvedovsky E, Peleg R, Vardy DA. Similarities between neuropathic pruritus sites and lichen simplex chronicus sites. Isr Med Assoc J. 2014;16(2):88–90.PubMedGoogle Scholar
  12. 12.
    Eisen A. The use of somatosensory evoked potentials for the evaluation of the peripheral nervous system. Neurol Clin. 1988;6(4):825–38.PubMedGoogle Scholar
  13. 13.
    Kim SM, Kim SH, Seo DW, Lee KW. Intraoperative neurophysiologic monitoring: basic principles and recent update. J Korean Med Sci. 2013;28(9):1261–9.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Yudina MM, Toropina GG, Lvov A, Gieler U. Innovative neurophysiological methods in itch research: long-latency evoked potentials after electrical and thermal stimulation in patients with atopic dermatitis. Acta Derm Venereol. 2011;91(6):656–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Mochizuki H, Inui K, Yamashiro K, Ootsuru N, Kakigi R. Itching-related somatosensory evoked potentials. Pain. 2008;138(3):598–603.CrossRefPubMedGoogle Scholar
  16. 16.
    Filevich E, Haggard P. Grin and bear it! Neural consequences of a voluntary decision to act or inhibit action. Exp Brain Res. 2012;223(3):341–51.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hansson P, Backonja M, Bouhassira D. Usefulness and limitations of quantitative sensory testing: clinical and research application in neuropathic pain states. Pain. 2007;129(3):256–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Walk D, Sehgal N, Moeller-Bertram T, Edwards RR, Wasan A, Wallace M, Irving G, Argoff C, Backonja MM. Quantitative sensory testing and mapping: a review of nonautomated quantitative methods for examination of the patient with neuropathic pain. Clin J Pain. 2009;25(7):632–40.CrossRefPubMedGoogle Scholar
  19. 19.
    Demant DT, Lund K, Vollert J, Maier C, Segerdahl M, Finnerup NB, Jensen TS, Sindrup SH. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study. Pain. 2014;155(11):2263–73.CrossRefPubMedGoogle Scholar
  20. 20.
    Mainka T, Malewicz NM, Baron R, Enax-Krumova EK, Treede RD, Maier C. Presence of hyperalgesia predicts analgesic efficacy of topically applied capsaicin 8% in patients with peripheral neuropathic pain. Eur J Pain. 2015;20(1):116–29.Google Scholar
  21. 21.
    Grosen K, Fischer IW, Olesen AE, Drewes AM. Can quantitative sensory testing predict responses to analgesic treatment? Eur J Pain. 2013;17(9):1267–80.CrossRefPubMedGoogle Scholar
  22. 22.
    Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magerl W, Maihofner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B. Quantitative sensory testing in the German research network on neuropathic pain (DFNS): standardized protocol and reference values. Pain. 2006;123(3):231–43.CrossRefPubMedGoogle Scholar
  23. 23.
    Maier C, Baron R, Tolle TR, Binder A, Birbaumer N, Birklein F, Gierthmuhlen J, Flor H, Geber C, Huge V, Krumova EK, Landwehrmeyer GB, Magerl W, Maihofner C, Richter H, Rolke R, Scherens A, Schwarz A, Sommer C, Tronnier V, Uceyler N, Valet M, Wasner G, Treede RD. Quantitative sensory testing in the German research network on neuropathic pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain. 2010;150(3):439–50.CrossRefPubMedGoogle Scholar
  24. 24.
    Magerl W, Krumova EK, Baron R, Tolle T, Treede RD, Maier C. Reference data for quantitative sensory testing (QST): refined stratification for age and a novel method for statistical comparison of group data. Pain. 2010;151(3):598–605.CrossRefPubMedGoogle Scholar
  25. 25.
    Pfau DB, Krumova EK, Treede RD, Baron R, Toelle T, Birklein F, Eich W, Geber C, Gerhardt A, Weiss T, Magerl W, Maier C. Quantitative sensory testing in the German research network on neuropathic pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia. Pain. 2014;155(5):1002–15.CrossRefPubMedGoogle Scholar
  26. 26.
    Brenaut E, Marcorelles P, Genestet S, Menard D, Misery L. Pruritus: an underrecognized symptom of small-fiber neuropathies. J Am Acad Dermatol. 2015;72(2):328–32.CrossRefPubMedGoogle Scholar
  27. 27.
    Stumpf A, Stander S. Neuropathic itch: diagnosis and management. Dermatol Ther. 2013;26(2):104–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Merkies IS, Faber CG, Lauria G. Advances in diagnostics and outcome measures in peripheral neuropathies. Neurosci Lett. 2015;596:3–13.CrossRefPubMedGoogle Scholar
  29. 29.
    Panoutsopoulou IG, Wendelschafer-Crabb G, Hodges JS, Kennedy WR. Skin blister and skin biopsy to quantify epidermal nerves: a comparative study. Neurology. 2009;72(14):1205–10.CrossRefPubMedGoogle Scholar
  30. 30.
    Wang L, Hilliges M, Jernberg T, Wiegleb-Edstrom D, Johansson O. Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin. Cell Tissue Res. 1990;261(1):25–33.CrossRefPubMedGoogle Scholar
  31. 31.
    Lauria G, Bakkers M, Schmitz C, Lombardi R, Penza P, Devigili G, Smith AG, Hsieh ST, Mellgren SI, Umapathi T, Ziegler D, Faber CG, Merkies IS. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010;15(3):202–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Lauria G, Dacci P, Lombardi R, Cazzato D, Porretta-Serapiglia C, Taiana M, Sassone J, Dalla Bella E, Rinaldo S, Lettieri C, Eleopra R, Devigili G. Side and time variability of intraepidermal nerve fiber density. Neurology. 2015;84(23):2368–71.CrossRefPubMedGoogle Scholar
  33. 33.
    Vlckova-Moravcova E, Bednarik J, Dusek L, Toyka KV, Sommer C. Diagnostic validity of epidermal nerve fiber densities in painful sensory neuropathies. Muscle Nerve. 2008;37(1):50–60.CrossRefPubMedGoogle Scholar
  34. 34.
    Schuhknecht B, Marziniak M, Wissel A, Phan NQ, Pappai D, Dangelmaier J, Metze D, Stander S. Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy. Br J Dermatol. 2011;165(1):85–91.CrossRefPubMedGoogle Scholar
  35. 35.
    Maddison B, Parsons A, Sangueza O, Sheehan DJ, Yosipovitch G. Retrospective study of intraepidermal nerve fiber distribution in biopsies of patients with nummular eczema. Am J Dermatopathol. 2011;33(6):621–3.CrossRefPubMedGoogle Scholar
  36. 36.
    Huesmann T, Cunha PR, Osada N, Huesmann M, Zanelato TP, Phan NQ, Gontijo GM, Marziniak M, Stander S. Notalgia paraesthetica: a descriptive two-cohort study of 65 patients from Brazil and Germany. Acta Derm Venereol. 2012;92(5):535–40.CrossRefPubMedGoogle Scholar
  37. 37.
    Papanas N, Ziegler D. Corneal confocal microscopy: a new technique for early detection of diabetic neuropathy. Curr Diab Rep. 2013;13(4):488–99.CrossRefPubMedGoogle Scholar
  38. 38.
    Jalbert I, Stapleton F, Papas E, Sweeney DF, Coroneo M. In vivo confocal microscopy of the human cornea. Br J Ophthalmol. 2003;87(2):225–36.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Tavakoli M, Petropoulos IN, Malik RA. Corneal confocal microscopy to assess diabetic neuropathy: an eye on the foot. J Diabetes Sci Technol. 2013;7(5):1179–89.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Malik RA, Kallinikos P, Abbott CA, van Schie CH, Morgan P, Efron N, Boulton AJ. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia. 2003;46(5):683–8.PubMedGoogle Scholar
  41. 41.
    Tavakoli M, Quattrini C, Abbott C, Kallinikos P, Marshall A, Finnigan J, Morgan P, Efron N, Boulton AJ, Malik RA. Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care. 2010;33(8):1792–7.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Midena E, Brugin E, Ghirlando A, Sommavilla M, Avogaro A. Corneal diabetic neuropathy: a confocal microscopy study. J Refract Surg. 2006;22(9 Suppl):S1047–52.PubMedGoogle Scholar
  43. 43.
    Erie JC, McLaren JW, Hodge DO, Bourne WM. The effect of age on the corneal subbasal nerve plexus. Cornea. 2005;24(6):705–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Messmer EM, Schmid-Tannwald C, Zapp D, Kampik A. In vivo confocal microscopy of corneal small fiber damage in diabetes mellitus. Graefes Arch Clin Exp Ophthalmol. 2010;248(9):1307–12.CrossRefPubMedGoogle Scholar
  45. 45.
    Dahan A, Dunne A, Swartjes M, Proto PL, Heij L, Vogels O, van Velzen M, Sarton E, Niesters M, Tannemaat MR, Cerami A, Brines M. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med. 2013;19:334–45.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    De Clerck EE, Schouten JS, Berendschot TT, Kessels AG, Nuijts RM, Beckers HJ, Schram MT, Stehouwer CD, Webers CA. New ophthalmologic imaging techniques for detection and monitoring of neurodegenerative changes in diabetes: a systematic review. Lancet Diabetes Endocrinol. 2015;3(8):653–63.CrossRefPubMedGoogle Scholar
  47. 47.
    Asghar O, Petropoulos IN, Alam U, Jones W, Jeziorska M, Marshall A, Ponirakis G, Fadavi H, Boulton AJ, Tavakoli M, Malik RA. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care. 2014;37(9):2643–6.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Tavakoli M, Kallinikos P, Iqbal A, Herbert A, Fadavi H, Efron N, Boulton AJ, Malik RA. Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy. Diabet Med. 2011;28(10):1261–7.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Donadio V, Liguori R. Microneurographic recording from unmyelinated nerve fibers in neurological disorders: an update. Clin Neurophysiol. 2015;126(3):437–45.CrossRefPubMedGoogle Scholar
  50. 50.
    Handwerker HO. Microneurography of pruritus. Neurosci Lett. 2010;470(3):193–6.CrossRefPubMedGoogle Scholar
  51. 51.
    Namer B, Carr R, Johanek LM, Schmelz M, Handwerker HO, Ringkamp M. Separate peripheral pathways for pruritus in man. J Neurophysiol. 2008;100(4):2062–9.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Valeriani M, Pazzaglia C, Cruccu G, Truini A. Clinical usefulness of laser evoked potentials. Neurophysiol Clin. 2012;42(5):345–53.CrossRefPubMedGoogle Scholar
  53. 53.
    Pazzaglia C, Vollono C, Ferraro D, Virdis D, Lupi V, Le Pera D, Tonali P, Padua L, Valeriani M. Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1 A: a laser-evoked potential study. Pain. 2010;149(2):379–85.CrossRefPubMedGoogle Scholar
  54. 54.
    Quante M, Lorenz J, Hauck M. Laser-evoked potentials: prognostic relevance of pain pathway defects in patients with acute radiculopathy. Eur Spine J. 2010;19(2):270–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Truini A, Galeotti F, Haanpaa M, Zucchi R, Albanesi A, Biasiotta A, Gatti A, Cruccu G. Pathophysiology of pain in postherpetic neuralgia: a clinical and neurophysiological study. Pain. 2008;140(3):405–10.CrossRefPubMedGoogle Scholar
  56. 56.
    Agostino R, Cruccu G, Romaniello A, Innocenti P, Inghilleri M, Manfredi M. Dysfunction of small myelinated afferents in diabetic polyneuropathy, as assessed by laser evoked potentials. Clin Neurophysiol. 2000;111(2):270–6.CrossRefPubMedGoogle Scholar
  57. 57.
    Pozzessere G, Rossi P, Gabriele A, Cipriani R, Morocutti A, Di Mario U, Morano S. Early detection of small-fiber neuropathy in diabetes: a laser-induced pain somatosensory-evoked potentials and pupillometric study. Diabetes Care. 2002;25(12):2355–8.CrossRefPubMedGoogle Scholar
  58. 58.
    Garcia-Larrea L, Perchet C, Creac’h C, Convers P, Peyron R, Laurent B, Mauguiere F, Magnin M. Operculo-insular pain (parasylvian pain): a distinct central pain syndrome. Brain. 2010;133(9):2528–39.CrossRefPubMedGoogle Scholar
  59. 59.
    de Tommaso M, Valeriani M, Guido M, Libro G, Specchio LM, Tonali P, Puca F. Abnormal brain processing of cutaneous pain in patients with chronic migraine. Pain. 2003;101(1–2):25–32.CrossRefPubMedGoogle Scholar
  60. 60.
    de Tommaso M, Federici A, Santostasi R, Calabrese R, Vecchio E, Lapadula G, Iannone F, Lamberti P, Livrea P. Laser-evoked potentials habituation in fibromyalgia. J Pain. 2011;12(1):116–24.CrossRefPubMedGoogle Scholar
  61. 61.
    Spiegel J, Hansen C, Baumgartner U, Hopf HC, Treede RD. Sensitivity of laser-evoked potentials versus somatosensory evoked potentials in patients with multiple sclerosis. Clin Neurophysiol. 2003;114(6):992–1002.CrossRefPubMedGoogle Scholar
  62. 62.
    Katsarava Z, Ayzenberg I, Sack F, Limmroth V, Diener HC, Kaube H. A novel method of eliciting pain-related potentials by transcutaneous electrical stimulation. Headache. 2006;46(10):1511–7.CrossRefPubMedGoogle Scholar
  63. 63.
    Kodaira M, Inui K, Kakigi R. Evaluation of nociceptive Adelta- and C-fiber dysfunction with lidocaine using intraepidermal electrical stimulation. Clin Neurophysiol. 2014;125(9):1870–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag London 2016

Authors and Affiliations

  • Esther Pogatzki-Zahn
    • 1
    Email author
  • Manuel P. Pereira
    • 1
    • 2
  • Martin Tegenthoff
    • 3
  1. 1.Department of Anesthesiology, Intensive Care and Pain MedicineUniversity Hospital MünsterMünsterGermany
  2. 2.Department of Dermatology and Center for Chronic PruritusUniversity Hospital MünsterMünsterGermany
  3. 3.Department of NeurologyBG-University Hospital – Ruhr-UniversityBochumGermany

Personalised recommendations