Courtesy of the Science Photo Library.

Itch sensations — for example, those produced by a mosquito bite — are familiar to us all. In most cases, itch is a temporary annoyance that might prompt action to avoid the cause in the future. But for people suffering from clinically intractable itch as a result of atopic dermatitis, liver disease or immune system disorders, it is a serious problem. However, a lack of understanding of the neural nature of itch has hindered the development of adequate therapies. So the discovery by Andrew and Craig of a class of itch-specific spinothalamic tract (STT) neurons, described in Nature Neuroscience , is an important breakthrough.

An itch-specific neural pathway has long been an attractive hypothesis to explain itch, but results to support this idea have been elusive. The first evidence was provided by the identification in humans of primary afferent C-fibres that selectively responded to histamine (the best-known itch inducer in skin) in a manner that parallels the sensation of itch. These neurons were insensitive to mechanical and thermal stimuli, and had very low conduction velocities. Andrew and Craig reasoned that if itch is a specific sensation, then the specificity of histamine-selective primary afferent fibres should be represented centrally.

Lesion studies have indicated that the pathway for itch — like that for pain — involves the STT, which projects to the thalamus. Functionally and morphologically selective STT neurons are located in lamina I of the spinal cord. By implanting thalamic electrodes in anaesthetized cats, the authors activated and thus identified lamina I STT neurons that projected to the thalamus. They then systematically categorized these neurons according to their response to mechanical and thermal stimulation of their innveration area in the skin. Most were conventional nociceptive-specific, thermoreceptive-specific or polymodal nociceptive neurons, but a small fraction (17/190) showed no response at all (14) or only a weak response to noxious heat (3). The activity of each of the insensitive neurons was monitored when histamine was applied to their innervation area, and ten were excited with a response pattern that corresponded to the histamine-sensitive C-fibre activity in humans and the accompanying itch sensations. Conventional STT neurons did not show this response. The itch-specific neurons also differed in other physiological properties — they had low conduction velocities, did not show spontaneous activity and projected predominantly to the lateral thalamus. These data indicate that the identified itch-specific neurons constitute a functionally and anatomically distinct group of STT neurons that provides a central neural substrate for itch.

Furthermore, it was shown that these itch-specific neurons were monosynaptically activated only by C-fibres with very low conduction velocities similar to those of the histamine-selective C-fibres in humans. So it seems that itch is mediated by specific peripheral and central pathways. Interestingly, various observations indicate that itch pathways interact with those for pain — for example, scratching inhibits itch and opiate administration reduces pain but can cause itch. Further understanding of itch pathways and their interactions will hopefully lead to new treatments for clinically intractable itch.