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Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
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Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV interneuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury.
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“The Cdh3 dorsal, inhibitory family was comprised of Inhib-6, Inhib-7, and Inhib-8 and are likely to be involved in the dampening of dynamic touch and therefore in mechanical allodynia70–72.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [72]
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Metadata
- Authors
- Petitjean, H., Pawlowski, S. A., Fraine, S. L., Sharif, B., Hamad, D., Fatima, T., Berg, J., Brown, C. M., Jan, L.-Y., Ribeiro-da-Silva, A., Braz, J. M., Basbaum, A. I., & Sharif-Naeini, R.
- Affiliations
- McGill University (CA)
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 13
- Issue
- 6
- Pages
- 1246-1257
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6038918
- OpenAlex
- W2132809690
- Cited by
- 326
- References
- 58
- Citations by year
- 2026: 28 · 2025: 14 · 2024: 22 · 2023: 41 · 2022: 38 · 2021: 34 · 2020: 42 · 2019: 38 · 2018: 28 · 2017: 23 · 2016: 18
- FWCI
- 16.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship@McGill (McGill) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust (102645, 102645/Z/13/Z)
- Canadian Institutes of Health Research (MOP79411)
- National Institute on Drug Abuse (R01DA029204, R01DA29204)
- National Institute of Neurological Disorders and Stroke (R01NS069229, R37NS14627, R01NS014627, R37NS014627)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- neuropathic pain, parvalbumin interneurons, dorsal horn, spinal cord, disinhibition, mechanical allodynia, mechanical hypersensitivity, nerve injury, inhibitory interneurons, neuronal ablation
- MeSH terms
- Animals, Cells, Cultured, Hyperalgesia, Interneurons, Neuralgia, Parvalbumins, Protein Kinase C, Synapses, Touch, Mice, Spinal Cord Dorsal Horn
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