Dynorphin Acts as a Neuromodulator to Inhibit Itch in the Dorsal Horn of the Spinal Cord
Open accessAbstract
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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The Pdyn dorsal inhibitory family comprised Inhib-9, Inhib-10, and Inhib-11 and expressed markers suggestive of a role in chemical itch.
“The Pdyn dorsal, inhibitory family was comprised of Inhib-9, Inhib-10, and Inhib-11 and expressed markers suggestive of a role in chemical itch52,61,73–77.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [76]
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- Authors
- Kardon, A. P., Polgár, E., Hachisuka, J., Snyder, L. M., Cameron, D., Savage, S., Cai, X., Karnup, S., Fan, C. R., Hemenway, G. M., Bernard, C. S., Schwartz, E. S., Nagase, H., Schwarzer, C., Watanabe, M., Furuta, T., Kaneko, T., Koerber, H. R., Todd, A. J., & Ross, S. E.
- Affiliations
- University of Pittsburgh (US)
- University of Glasgow (GB)
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA) (JP)
- Innsbruck Medical University (AT)
- Hokkaido University (JP)
- Kyoto University (JP)
- Corresponding author
- Todd, Andrew J.
- Ross, Sarah E.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 82
- Issue
- 3
- Pages
- 573-586
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4022838
- OpenAlex
- W2163039776
- Cited by
- 369
- References
- 91
- Citations by year
- 2026: 30 · 2025: 23 · 2024: 22 · 2023: 26 · 2022: 29 · 2021: 30 · 2020: 35 · 2019: 39 · 2018: 33 · 2017: 27 · 2016: 26 · 2015: 37 · 2014: 10 · 2013: 1
- FWCI
- 22.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Neuron (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Funders
- Rita Allen Foundation
- Allen Foundation
- Wellcome Trust
- National Institutes of Health (UL1TR000005)
- Medical Research Council (MR/L003430/1)
- Biotechnology and Biological Sciences Research Council (BB/J001082/1, BB/J001082)
- National Institute of General Medical Sciences (T34GM087239)
- National Institute of Neurological Disorders and Stroke (R01NS023725, T32NS073548)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR064445, R01AR063772)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- dynorphin, pruritus, dorsal horn, spinal cord, menthol, kappa opioid receptor, sensory neurons, capsaicin, mustard oil, neuromodulation
- MeSH terms
- Analgesics, Opioid, Animals, Capsaicin, Dynorphins, Interneurons, Male, Mice, Inbred C57BL, Neural Inhibition, Organ Culture Techniques, Pruritus, Spinal Cord, Octreotide, Receptors, Opioid, kappa, Mice, Knockout, Posterior Horn Cells, Mice
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