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Dr Ben Seymour, Computational and Biological Learning Lab, Trumpington Street, Cambridge CB2 1PZ

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Center for Information and Neural Networks, National Institute for Information and Communications Technology (NICT), 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.

bjs49 AT cam.ac.uk / seymour AT cinet.jp

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Monday
Apr152013

Itchy neurons... 

ITCH is one of the most curious of sensations - it's hard to know how you would describe it if we didn't have the word 'itch'. On one hand it's aversive, and indeed for patients with severe itch due to skin or neurological disorders, it is nothing short of pure torment. But for most of us, it is also enormously satisfying to scratch - indeed arguably much more satisfying than the original itch was unpleasant (compare it with pain and pain relief for instance). Itch also has the remarkable capacity to be induced by seeing someone else scratching. Actually just reading the word itch will make you itch (if you've read this far, you've almost certainly scratched at least once).

The yin-and-yang of averision and relief is paralelled in many of the so-called interoceptive sensations, signaling the departure and back of a variety of homeostatic states. And these are typically signalled but what has traditionally been considered the pain and temperature pathway, mediated in the peripheral mostly by a humble but fascinating group of small unmyelinated neurons: c-fibers. The c-fiber was long considered the poor mans sensory fiber, but their true sophistication and diversity is only now fully emerging. Incorporating sensations such as warmth, pain, itch, tickle and sensual touch, they convey a plethora of interoceptive sensations that support a phenomenological richness that their large myelinated cousins could only dream of. The story of their ascendancy is framed in one of the great debates of modern neuroscience - the ‘labeled line hypothesis’. In brief, do these experientially different sensations have their own dedicated neural pathways peripherally and centrally, or do they share a common set of pathways that are decoded by the brain. Or is the answer somewhere in between, involving an intermediate degree of afferent specificity.

The ‘itch-line’ hypothesis has been highlighted by a number of seminal papers: Schmelz and colleagues discovery of a specific subpopulation of histamine responsive c-fibers who’s responses correlated with the perceptual evolution of itch after histamine administration [1]; Andrew and Craig’s identification of a specific itch responsive spinothalamic tract neurons in the cat [2]; and Sun and colleagues discovery of a population of gastrin-releasing peptide receptor lamina 1 dorsal horn neurons selectively involved in itch [3].

Now, Han and colleagues report a population of MrgprA3 expressing c-fibers that seem to be specific for non-histamine involving itch. Ablation of these fibers resulted in reduction of itch to a range of itch stimuli, but importantly, not pain. Furthermore, activation of TRPV1 co-expressing MrgprA3 fibers induced itch but not pain behaviour.

Together, these findings elucidate a new population of non-histaminergic itch c-fibers, suggesting a highly selective itch-line pathway, and a new target for clinical interventions.

  

[1] Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjörk HE. Specific C-receptors for itch in human skin. J Neurosci 1997; 17: 8003–8008.

[2] Andrew D, Craig AD. Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nat Neurosci 2001; 4: 72–77.

[3] Sun Y-G, Chen Z-F. A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature 2007; 448: 700–703.

Based on a recently published F1000 post-publication peer review with Hiro Mano

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