A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior
Open accessAbstract
Significance: Neuropathic pain is a debilitating chronic pain condition occurring after nerve damage. Its cardinal symptom is touch-evoked pain (mechanical allodynia), which is refractory to available medications including morphine. The underlying mechanism for allodynia remains incompletely understood. Using our recently established optogenetic approach for allodynia, here we identify a subset of spinal dorsal horn inhibitory interneurons (AAV-NpyP + interneurons) that acts as a critical brake on conversion of touch-sensing Aβ fiber signals into pain-like behavior that is resistant to morphine. AAV-NpyP + interneuron activity was reduced in a neuropathic pain model, and, conversely, activation of AAV-NpyP + interneurons in this model reversed Aβ fiber-derived pain-like behavior. Our study reveals a mechanism for touch–pain conversion and may provide a therapeutic strategy for neuropathic allodynia.
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The Npy dorsal inhibitory family comprised Inhib-12 and Inhib-13; studies suggest this family's markers identify neurons involved in mechanical itch and pain.
“The Npy dorsal, the inhibitory family was comprised of Inhib-12 and Inhib-13. Studies suggest this family’s markers identify neurons involved in mechanical itch and pain73,78,79.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [79]
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References 56 · Cited by 54
- Authors
- Tashima, R., Koga, K., Yoshikawa, Y., Sekine, M., Watanabe, M., Tozaki-Saitoh, H., Furue, H., Yasaka, T., & Tsuda, M.
- Affiliations
- Kyushu University (JP)
- Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, 812-8582 Fukuoka, Japan;
- Hyogo Medical University (JP)
- Kagoshima University (JP)
- Corresponding author
- Tashima, Ryoichi
- Koga, Keisuke
- Yoshikawa, Yu
- Yasaka, Toshiharu
- Tsuda, Makoto
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-01-11
- Volume
- 118
- Issue
- 3
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7826356
- OpenAlex
- W3120238312
- Cited by
- 54
- References
- 56
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 7 · 2023: 9 · 2022: 16 · 2021: 5
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (18K07394, 20K16133, 19H05658)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- neuropathic pain, mechanical allodynia, inhibitory interneurons, neuropeptide Y, optogenetics, Aβ fibers
- MeSH terms
- Animals, gamma-Aminobutyric Acid, Hyperalgesia, Interneurons, Male, Mechanoreceptors, Neuralgia, Protein Kinase C, Touch, Posterior Horn Cells, Rats, Touch Perception, Nociception, Peripheral Nerve Injuries, Spinal Cord Dorsal Horn
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