Neuron
Volume 82, Issue 3, 7 May 2014, Pages 573-586
Journal home page for Neuron

Article
Dynorphin Acts as a Neuromodulator to Inhibit Itch in the Dorsal Horn of the Spinal Cord

https://doi.org/10.1016/j.neuron.2014.02.046Get rights and content
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Highlights

  • Spinal B5-I interneurons function to inhibit itch

  • B5-I neurons release the kappa opioid dynorphin

  • Kappa opioid signaling bidirectionally modulates itch within the spinal cord

  • Spinal B5-I interneurons mediate the inhibition of itch by menthol

Summary

Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5−/− mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

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Co-first authors