Elsevier

The Lancet

Volume 361, Issue 9358, 22 February 2003, Pages 690-694
The Lancet

Review
Itch

https://doi.org/10.1016/S0140-6736(03)12570-6Get rights and content

Summary

Itch is a common skin sensation, with substantial effects on behaviour. Neurophysiological research has permitted accurate definition of neural pathways of itch, and has confirmed the distinctiveness of itch pathways in comparison with pain. A clinical classification of itch, based on such improved understanding, describes the difference between peripheral (pruritoceptive) and central (neurogenic or neuropathic) itch. New specific and sensitive investigational methods in people and animals enable us to better understand this bothersome symptom, and have important clinical implications. We describe the clinical classification of itch, new findings on neuropathophysiology of itch, methods for assessment, and improved treatments.

Section snippets

Definitions, types, and clinical classification

Itch has many similarities to pain.2 Both are unpleasant sensory experiences, but the behavioural response patterns differ—pain elicits a reflex withdrawal, whereas itch leads to a scratch reflex. However, both can lead to serious impairment of quality of life.

A stimulus causing itch leads to two distinct responses: 3 first, a well localised itch at the site of the stimulus, which persists only briefly after the stimulus has been removed; and second, a subsequent diffuse poorly localised area

Neuronal pathways

Findings of investigations with direct nerve recordings in awake individuals have shown that itch is transmitted by dedicated C neurons, which are distinct from the polymodal nociceptors that are implicated in pain processing. These itch neurons can be identified by their lasting response to histamine application, and are characterised by their slow conduction velocities and extensive terminal branching.7 The idea of dedicated itch neurons has now been complemented and extended by studies of

Scratching and rubbing

Scratching and rubbing the skin inhibits itch (surround inhibition).15 These activities stimulate myelinated A neurons via low threshold mechanoreceptors, which excite presynaptic and postsynaptic mechanisms to inhibit neuronal circuits in the grey matter of the spinal cord, and lead to temporary suppression of itching. Scratching also activates nociceptors, which also reduces itch via the spine, since pain inhibits itch. There have been several practical applications of this observation, such

Protease-activated receptors and the action of capsaicin

The proximity of dermal mast cells to afferent C neuron terminals in skin suggests a functional relation between these two cell types. Human dermal mast cells express two proteases: tryptase and chymase. Steinhoff and colleagues19 have proposed a link between mast cell tryptase and excitation of nociceptors in rat skin. Activation of the mast cell releases tryptase, which in turn activates proteinase activated receptor-2 (PAR-2) localised on C fibre nerve terminals. The activated C fibres will

Animal models

The main obstacle for development of animal models of itch is that scratching behaviour in animals is a regular occurrence and might not be a true indicator of itch. Behavioural data suggest that intradermal injection of substances that induce itch in man lead to dose-related hindlimb scratching in rodents, which could be distinguished from responses to pain.26, 27 This model is of potential benefit for studies of itch physiology. However, in view of the large differences in skin sensitivity

Itch in skin and systemic diseases

Itch is a common and important symptom of systemic disease, but is frequently difficult to control. It is often multifactorial, involving pruritoceptive components such as skin dryness, as well as neurogenic factors. However, advances in understanding of pathophysiology and molecular mechanisms have in some instances improved treatment.

Evaluation of symptoms

A detailed conventional history and thorough examination are all important, but a detailed description of the qualitative, temporal, and spatial characteristics of itch symptoms should also be obtained from the patient. Two itch questionnaires57, 58 to help to assess these components have been validated, both based on the well recognised McGill pain questionnaire. One is based on the long form of the McGill questionnaire, and covers in detail sensory descriptors of itch; the other resembles the

Treatment

Improved understanding of the pathophysiology of itch has led to modest advances in treatment. No doubt in time this progress will lead to selective topical antipruritics. Topical corticosteroids are not direct antipruritics and should not be used as such, although they effectively relieve itching secondary to inflammatory skin disease. Antipruritic strategies could be assigned according to proposed classification of itch. Therapeutics mainly targeting pruritoceptive itch consist of topical

Search strategy

We searched Medline in July, 2002, with the key words itch and pruritus, and obtained data from reports in peer reviewed journals, book reference lists, and findings presented at the International Workshop for the Study of Itch in Singapore (2001).

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