The neurology of itch

Brain. 2014 Feb;137(Pt 2):313-22. doi: 10.1093/brain/awt158. Epub 2013 Jun 22.


Research over the past 15 years has helped to clarify the anatomy and physiology of itch, the clinical features of neuropathic itch syndromes and the scientific underpinning of effective treatments. Two itch-sensitive pathways exist: a histamine-stimulated pathway that uses mechanically insensitive C-fibres, and a cowhage-stimulated pathway primarily involving polymodal C-fibres. Interactions with pain continue to be central to explaining various aspects of itch. Certain spinal interneurons (Bhlhb5) inhibit itch pathways within the dorsal horn; they may represent mediators between noxious and pruritic pathways, and allow scratch to inhibit itch. In the brain, functional imaging studies reveal diffuse activation maps for itch that overlap, but not identically, with pain maps. Neuropathic itch syndromes are chronic itch states due to dysfunction of peripheral or central nervous system structures. The most recognized are postherpetic itch, brachioradial pruritus, trigeminal trophic syndrome, and ischaemic stroke-related itch. These disorders affect a patient's quality of life to a similar extent as neuropathic pain. Treatment of neuropathic itch focuses on behavioural interventions (e.g., skin protection) followed by stepwise trials of topical agents (e.g., capsaicin), antiepileptic drugs (e.g., gabapentin), injection of other agents (e.g., botulinum A toxin), and neurostimulation techniques (e.g., cutaneous field stimulation). The involved mechanisms of action include desensitization of nerve fibres (in the case of capsaicin) and postsynaptic blockade of calcium channels (for gabapentin). In the future, particular histamine receptors, protease pathway molecules, and vanilloids may serve as targets for novel antipruritic agents.

Keywords: afferent pathways; itch; itch therapy; pruritus.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Benzamidines
  • Guanidines / pharmacology
  • Guanidines / therapeutic use
  • Histamine / physiology
  • Histamine Antagonists / pharmacology
  • Histamine Antagonists / therapeutic use
  • Humans
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / physiology
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / physiopathology*
  • Nervous System Diseases / therapy
  • Pruritus / diagnosis
  • Pruritus / physiopathology*
  • Pruritus / therapy
  • Spinothalamic Tracts / drug effects
  • Spinothalamic Tracts / physiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzamidines
  • Guanidines
  • Histamine Antagonists
  • Histamine
  • nafamostat