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Neuron. 2014 May 7;82(3):573-86. doi: 10.1016/j.neuron.2014.02.046. Epub 2014 Apr 10.

Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.

Author information

1
Department of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
2
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
3
Department of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
4
University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
5
International Institute for Integrative Sleep Medicine, University of Tsukuba, Life Science Center of Tsukuba Advanced Research Alliance C-1F, 1-1-1 Tenoudai Tsukuba Ibaraki, Tsukuba 305-8577, Japan.
6
Department of Pharmacology, Innsbruck Medical University, A-6020 Innsbruck, Austria.
7
Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
8
Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
9
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. Electronic address: andrew.todd@glasgow.ac.uk.
10
Department of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Electronic address: saross@pitt.edu.

Abstract

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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PMID:
24726382
PMCID:
PMC4022838
DOI:
10.1016/j.neuron.2014.02.046
[Indexed for MEDLINE]
Free PMC Article
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