ABSTRACT
The neurophysiology of itch, the dominant symptom of skin disease, has previously received scant attention. Recent advances in the neurophysiology and molecular basis of itch include the use of microneurography to demonstrate the existence of a subset of itch-dedicated afferent C neurons distinct from neurons which transmit pain; use of functional positron emission tomography (PET) and magnetic resonance imaging (MRI) of the brain to reveal an itch-specific activation matrix, and new evidence of a functional "dialogue" between C neuron terminals and dermal mast cells in which recently described proteinase-activated receptor type 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors, proteases and endovanilloids play a major role. As a necessary prerequisite to diagnosis and management, a pathophysiologically based classification of itch is proposed. Recent advances in understanding of the pathomechanisms of itch of cholestasis include the role of opioids and opioid antagonists. Focusing on neurogenic itch (itch without visible rash), common causes are reviewed and guidelines for laboratory and radiological investigation are proposed. A stepwise approach to management of generalised itch is recommended, including broadband or narrow band ultraviolet (UV), tricyclics such as doxepin, opioid antagonists including naltrexone and selective serotonin reuptake inhibitors (SSRIs) such as paroxetine. For troublesome localised itches such as insect bite reactions, physical urticaria, lichen simplex chronicus or, less commonly, notalgia paraesthetica, brachioradial pruritus, local cooling devices which rely on the cooling action of dimethyl ethers on thermosensitive TRP voltage-sensitive ion channels are now commercially available for shortterm relief.