Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Disease mechanisms in neuropathic itch

Nature Clinical Practice Neurology volume 4, pages 329–337 (2008)Cite this article

Abstract

Itch, also known as pruritus, is an unpleasant cutaneous sensation that provokes the desire to scratch. Itch is a common symptom of inflammatory skin disorders, but it can also occur in neurological diseases associated with injury to nervous tissue, in the absence of any skin disease and without any notable physiological stimuli in the periphery. This 'neuropathic' type of itch occurs either in combination with neuropathic pain or independently and is thought to be underdiagnosed. In this Review, we describe the physiological characteristics of specific neuronal systems in the PNS and CNS that transmit and process pruriceptive information, and we consider pathological changes that occur in these systems after nerve lesions. We then introduce a classification system for itch and highlight the similarities and differences between neuropathic itch and neuropathic pain. A summary of neuropathic syndromes in the PNS and CNS that are associated with itch is presented. Finally, we propose appropriate treatment strategies for neuropathic itch, in view of the fact that this condition has different mechanisms of itch generation to other types of itch and consequently requires different therapies.

Key Points

  • Neuropathic itch is a common symptom after nerve lesions

  • Neuropathic itch can occur in combination with neuropathic pain or independently

  • Lesions in the PNS and the CNS can both give rise to neuropathic itch

  • There are striking similarities in the mechanisms of generation of neuropathic pain and neuropathic itch

  • Neuropathic itch is treated differently from itch in skin disorders

  • Antidepressants, anticonvulsants and topical capsaicin are treatment options for neuropathic itch

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Primary afferent pruriceptive and nociceptive neurons with their spinal connections.
Figure 2: Interaction between mechanoreceptive, pruriceptive and nociceptive neurons in the spinal cord: a hypothesis.

Similar content being viewed by others

References

  1. Rothman S (1941) Physiology of itching. Physiol Rev 21: 357–381

    Article  Google Scholar 

  2. Ikoma A et al. (2006) The neurobiology of itch. Nat Rev Neurosci 7: 535–547

    Article  CAS  PubMed  Google Scholar 

  3. Schmelz M et al. (2003) Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens. J Neurophysiol 89: 2441–2448

    Article  CAS  PubMed  Google Scholar 

  4. Schmelz M et al. (1997) Specific C-receptors for itch in human skin. J Neurosci 17: 8003–8008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ikoma A et al. (2005) Electrically evoked itch in humans. Pain 113: 148–154

    Article  PubMed  Google Scholar 

  6. Andrew D and Craig AD (2001) Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nat Neurosci 4: 72–77

    Article  CAS  PubMed  Google Scholar 

  7. Simone DA et al. (1991) Psychophysical studies of the itch sensation and itchy skin (“alloknesis”) produced by intracutaneous injection of histamine. Somatosens Mot Res 8: 271–279

    Article  CAS  PubMed  Google Scholar 

  8. Atanassoff PG et al. (1999) Enhancement of experimental pruritus and mechanically evoked dysesthesiae with local anesthesia. Somatosens Mot Res 16: 291–298

    Article  CAS  PubMed  Google Scholar 

  9. Baron R (2006) Mechanisms of disease: neuropathic pain—a clinical perspective. Nat Clin Pract Neurol 2: 95–106

    Article  PubMed  Google Scholar 

  10. Ward L et al. (1996) A comparison of the effects of noxious and innocuous counterstimuli on experimentally induced itch and pain. Pain 64: 129–138

    Article  CAS  PubMed  Google Scholar 

  11. Yosipovitch G et al. (2005) Noxious heat and scratching decrease histamine-induced itch and skin blood flow. J Invest Dermatol 125: 1268–1272

    Article  CAS  PubMed  Google Scholar 

  12. Nilsson HJ et al. (1997) Cutaneous field stimulation (CFS): a new powerful method to combat itch. Pain 71: 49–55

    Article  CAS  PubMed  Google Scholar 

  13. Mochizuki H et al. (2003) Imaging of central itch modulation in the human brain using positron emission tomography. Pain 105: 339–346

    Article  PubMed  Google Scholar 

  14. Szarvas S et al. (2003) Neuraxial opioid-induced pruritus: a review. J Clin Anesth 15: 234–239

    Article  CAS  PubMed  Google Scholar 

  15. Twycross R et al. (2003) Itch: scratching more than the surface. QJM 96: 7–26

    Article  CAS  PubMed  Google Scholar 

  16. Grewe M et al. (2000) Neurotrophin-4 production by human epidermal keratinocytes: increased expression in atopic dermatitis. J Invest Dermatol 114: 1108–1112

    Article  CAS  PubMed  Google Scholar 

  17. Steinhoff M et al. (2006) Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus. J Invest Dermatol 126: 1705–1718

    Article  CAS  PubMed  Google Scholar 

  18. Bergasa NV and Jones EA (1995) The pruritus of cholestasis: potential pathogenic and therapeutic implications of opioids. Gastroenterology 108: 1582–1588

    Article  CAS  PubMed  Google Scholar 

  19. Bergasa NV (2004) Treatment of the pruritus of cholestasis. Curr Treat Options Gastroenterol 7: 501–508

    Article  PubMed  Google Scholar 

  20. Mansour-Ghanaei F et al. (2006) Effect of oral naltrexone on pruritus in cholestatic patients. World J Gastroenterol 12: 1125–1128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jones EA and Bergasa NV (1990) The pruritus of cholestasis: from bile acids to opiate agonists. Hepatology 11: 884–887

    Article  CAS  PubMed  Google Scholar 

  22. Calikusu C et al. (2003) The relation of psychogenic excoriation with psychiatric disorders: a comparative study. Compr Psychiatry 44: 256–261

    Article  PubMed  Google Scholar 

  23. Trabert W (1995) 100 years of delusional parasitosis: meta-analysis of 1,223 case reports. Psychopathology 28: 238–246

    Article  CAS  PubMed  Google Scholar 

  24. Ständer S et al. (2007) Clinical classification of itch: a position paper of the International Forum for the Study of Itch. Acta Derm Venereol 87: 291–294

    Article  PubMed  Google Scholar 

  25. Binder A et al. (2008) A case of neuropathic brachioradial pruritus caused by cervical disc herniation. Nat Clin Pract Neurol [10.1038/ncpneuro0807]

  26. Galer BS and Jensen MP (1997) Development and preliminary validation of a pain measure specific to neuropathic pain: the Neuropathic Pain Scale. Neurology 48: 332–338

    Article  CAS  PubMed  Google Scholar 

  27. Oaklander AL et al. (2003) Herpes zoster itch: preliminary epidemiologic data. J Pain 4: 338–343

    Article  PubMed  Google Scholar 

  28. Dunphy FR et al. (1997) A phase I report of paclitaxel dose escalation combined with a fixed dose of carboplatin in the treatment of head and neck carcinoma. Cancer 79: 2016–2023

    Article  CAS  PubMed  Google Scholar 

  29. Singh F and Rudikoff D (2003) HIV-associated pruritus: etiology and management. Am J Clin Dermatol 4: 177–188

    Article  PubMed  Google Scholar 

  30. Weidemann F et al. (2008) Misleading terms in Anderson–Fabry disease. Eur J Clin Invest 38: 191–196

    Article  CAS  PubMed  Google Scholar 

  31. Savk E et al. (2000) Notalgia paresthetica: a study on pathogenesis. Int J Dermatol 39: 754–759

    Article  CAS  PubMed  Google Scholar 

  32. Cohen AD et al. (2003) Brachioradial pruritus: a symptom of neuropathy. J Am Acad Dermatol 48: 825–828

    Article  PubMed  Google Scholar 

  33. Wallengren J and Sundler F (2005) Brachioradial pruritus is associated with a reduction in cutaneous innervation that normalizes during the symptom-free remissions. J Am Acad Dermatol 52: 142–145

    Article  PubMed  Google Scholar 

  34. Wallengren J (2005) Neuroanatomy and neurophysiology of itch. Dermatol Ther 18: 292–303

    Article  PubMed  Google Scholar 

  35. Cohen AD et al. (2005) Neuropathic scrotal pruritus: anogenital pruritus is a symptom of lumbosacral radiculopathy. J Am Acad Dermatol 52: 61–66

    Article  PubMed  Google Scholar 

  36. Jacome D (1978) Phantom itching relieved by scratching phantom feet. JAMA 240: 2432

    Article  CAS  PubMed  Google Scholar 

  37. Lee SS et al. (2004) Pruritus, pain, and small nerve fiber function in keloids: a controlled study. J Am Acad Dermatol 51: 1002–1006

    Article  PubMed  Google Scholar 

  38. Metze D et al. (1997) Persistent pruritus after hydroxyethyl starch infusion therapy: a result of long-term storage in cutaneous nerves. Br J Dermatol 136: 553–559

    Article  CAS  PubMed  Google Scholar 

  39. Canavero S et al. (1997) Central neurogenic pruritus: a literature review. Acta Neurol Belg 97: 244–247

    CAS  PubMed  Google Scholar 

  40. Adreev VC and Petkov I (1975) Skin manifestations associated with tumours of the brain. Br J Dermatol 92: 675–678

    Article  CAS  PubMed  Google Scholar 

  41. King CA et al. (1982) Unilateral neurogenic pruritus: paroxysmal itching associated with central nervous system lesions. Ann Intern Med 97: 222–223

    Article  CAS  PubMed  Google Scholar 

  42. Shabtai H et al. (1996) Pruritus in Creutzfeldt–Jakob disease. Neurology 46: 940–941

    Article  CAS  PubMed  Google Scholar 

  43. Yamamoto M et al. (1981) Paroxysmal itching in multiple sclerosis: a report of three cases. J Neurol Neurosurg Psychiatry 44: 19–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sandyk R (1994) Paroxysmal itching in multiple sclerosis during treatment with external magnetic fields. Int J Neurosci 75: 65–71

    Article  CAS  PubMed  Google Scholar 

  45. Ostermann PO and Westerberg CE (1975) Paroxysmal attacks in multiple sclerosis. Brain 98: 189–202

    Article  CAS  PubMed  Google Scholar 

  46. Magilner D (2006) Localized cervical pruritus as the presenting symptom of a spinal cord tumor. Pediatr Emerg Care 22: 746–747

    Article  PubMed  Google Scholar 

  47. Dey DD et al. (2005) Central neuropathic itch from spinal-cord cavernous hemangioma: a human case, a possible animal model, and hypotheses about pathogenesis. Pain 113: 233–237

    Article  PubMed  Google Scholar 

  48. Oaklander AL et al. (2002) Intractable postherpetic itch and cutaneous deafferentation after facial shingles. Pain 96: 9–12

    Article  PubMed  Google Scholar 

  49. Bernhard JD (2005) Itch and pruritus: what are they, and how should itches be classified. Dermatol Ther 18: 288–291

    Article  PubMed  Google Scholar 

  50. Baron R et al. (2001) Histamine-induced itch converts into pain in neuropathic hyperalgesia. Neuroreport 12: 3475–3478

    Article  CAS  PubMed  Google Scholar 

  51. Schmelz M (2006) Complex interactions between pain and itch. Pain 124: 9–10

    Article  CAS  PubMed  Google Scholar 

  52. Biro T et al. (2007) TRP channels as novel players in the pathogenesis and therapy of itch. Biochim Biophys Acta 1772: 1004–1021

    Article  CAS  PubMed  Google Scholar 

  53. Stander S et al. (2001) Treatment of prurigo nodularis with topical capsaicin. J Am Acad Dermatol 44: 471–478

    Article  CAS  PubMed  Google Scholar 

  54. Inoue K et al. (2002) Functional vanilloid receptors in cultured normal human epidermal keratinocytes. Biochem Biophys Res Commun 291: 124–129

    Article  CAS  PubMed  Google Scholar 

  55. Carstens E and Jinks SL (1998) Skin cooling attenuates rat dorsal horn neuronal responses to intracutaneous histamine. Neuroreport 9: 4145–4149

    Article  CAS  PubMed  Google Scholar 

  56. Savk E et al. (2001) Open pilot study on oxcarbazepine for the treatment of notalgia paresthetica. J Am Acad Dermatol 45: 630–632

    Article  CAS  PubMed  Google Scholar 

  57. Rogawski MA and Loscher W (2004) The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat Med 10: 685–692

    Article  CAS  PubMed  Google Scholar 

  58. Bueller HA et al. (1999) Gabapentin treatment for brachioradial pruritus. J Eur Acad Dermatol Venereol 13: 227–228

    Article  CAS  PubMed  Google Scholar 

  59. Yesudian PD and Wilson NJ (2005) Efficacy of gabapentin in the management of pruritus of unknown origin. Arch Dermatol 141: 1507–1509

    Article  CAS  PubMed  Google Scholar 

  60. Winhoven SM et al. (2004) Brachioradial pruritus: response to treatment with gabapentin. Br J Dermatol 150: 786–787

    Article  CAS  PubMed  Google Scholar 

  61. Taylor RS (1998) Multiple sclerosis potpourri: paroxysmal symptoms, seizures, fatigue, pregnancy, and more. Phys Med Rehabil Clin N Am 9: 551–559, vi

    Article  CAS  PubMed  Google Scholar 

  62. Zylicz Z et al. (2003) Paroxetine in the treatment of severe non-dermatological pruritus: a randomized, controlled trial. J Pain Symptom Manage 26: 1105–1112

    Article  CAS  PubMed  Google Scholar 

  63. Summey BT Jr and Yosipovitch G (2005) Pharmacologic advances in the systemic treatment of itch. Dermatol Ther 18: 328–332

    Article  PubMed  Google Scholar 

  64. Elkersh MA et al. (2003) Epidural clonidine relieves intractable neuropathic itch associated with herpes zoster-related pain. Reg Anesth Pain Med 28: 344–346

    CAS  PubMed  Google Scholar 

  65. Dawn AG and Yosipovitch G (2006) Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol 54: 527–531

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors' work is supported by the German Ministry of Research and Education, German Research Network on Neuropathic Pain (BMBF, 01EM01/04) and an unrestricted educational grant from Pfizer, Germany.

Author information

Authors and Affiliations

  1. A Binder is a Specialist Registrar and J Koroschetz is a Junior House Officer in the Division of Neurological Pain Research and Therapy, Department of Neurology, and R Baron is Head of the Division of Neurological Pain Research and Therapy and Vice Chair of the Department of Neurology, all at the Christian-Albrechts University of Kiel, Kiel, Germany. R Baron is also an Advisory Board member of Nature Clinical Practice Neurology.,

    Andreas Binder, Jana Koroschetz & Ralf Baron

Authors
  1. Andreas Binder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jana Koroschetz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ralf Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ralf Baron.

Ethics declarations

Competing interests

A Binder has received honoraria from Pfizer, Allergan and Grünenthal. R Baron has acted as a consultant and received honoraria and grant support from Genzyme and Pfizer, and has acted as a consultant and received honoraria from Allergan, Grünenthal, Medtronic, Mundipharma and Sanofi Pasteur MSD. J Koroschetz declared no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Binder, A., Koroschetz, J. & Baron, R. Disease mechanisms in neuropathic itch. Nat Rev Neurol 4, 329–337 (2008). https://doi.org/10.1038/ncpneuro0806

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpneuro0806

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing