The Vicious Itch-Scratch Cycle

How many times have you been told that “if you itch it’ll get worse”? Scratching an itch is satisfying in the short term, but actually prolongs the itch sensation due to neurological pathways involving serotonin, according to new research published in the journal Neuron.

Itching is undoubtedly a pleasurable sensation, and this has been scientifically verified using fMRI. Actively scratching an itch stimulates the reward centres of our brain that respond to pleasurable stimuli, although interestingly this is significantly reduced when the scratching is ‘passive’, ie., administered by someone else. The involvement of reward circuits explains the addictive nature of itch relief; however, a study in mice has now shown that prolonging the scratch will indeed prolong the itch.

As well as stimulating pleasure centres in the brain, scratching causes minor pain that inhibits an itch sensation. It also causes the release of serotonin (5-hydroxytryptophan: 5-HT), but as well as its role in pain mediation, this neurotransmitter also becomes involved in the itch pathway as it activates receptors involved in itch signalling.


Pain-Itch Cycle - photo credit Washington University Centre for the Study of Itch

Pain-Itch Cycle – photo credit Washington University Centre for the Study of Itch


The researchers have demonstrated for the first time that serotonin is involved in the itch-scratch cycle, mediated by central serotonin receptors found in the spinal cord. Loss-of-function studies in mice showed that without functioning 5-HT receptors, in particular 5-HT1A, the scratching response to an itch-causing chemical was significantly reduced. Injecting the precursor molecule for serotonin into mice without 5-HT receptors rescued the itch response, while in wild type mice this caused a striking increase in scratching. Further investigation showed this to depend on the gastrin-releasing peptide receptor (GRPR), which is known to mediate an itch-specific signalling pathway; activation of 5-HT1A increased the firing of GPRP+ neurons to augment the itch response.

The serotonin-based feedback systems in itch and pain neurological pathways cause a self-perpetuating itch-scratch progression: a painful and itchy vicious circle.


Zhao et al. (2014) Descending Control of Itch Transmission by the Serotonergic System via 5-HT1A-Facilitated GRP-GRPR Signaling. Neuron 84, 1-14. DOI:

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Veronica Wignall

Veronica is a Biology graduate from the University of Bristol, she is currently an editorial assistant but hopes to move into science media comms! Follow Veronica on Twitter @vronwig

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