Cited by 326Pain Mechanisms and TreatmentsIon Channels and ReceptorsPain Management and Treatment

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Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury

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Petitjean, Hugues, Pawlowski, Sophie Anne, Fraine, Steven Li, Sharif, Behrang, Hamad, Doulia, Fatima, Tarheen, Berg, Jim, Brown, Claire M., Jan, Lily-Yeh, Ribeiro-da-Silva, Alfredo, Braz, Joao M., Basbaum, Allan I., Sharif-Naeini, Reza·2015·Cell Reports

DOI 10.1016/j.celrep.2015.09.080PMC PMC6038918

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Abstract

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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Polgár, 2013, Functional differences between neurochemically defined populations of inhibitory interneurons in the rat spinal dorsal horn, Pain, 154, 2606, 10.1016/j.pain.2013.05.001 · DOI

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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: Petitjean, Hugues
Fraine, Steven Li
Sharif, Behrang
Hamad, Doulia
Berg, Jim
Brown, Claire M.
Jan, Lily-Yeh
Braz, Joao M.
Basbaum, Allan I.
Venue: Cell Reports
Publisher: Elsevier BV
Published: 2015-11
Volume: 13
Issue: 6
Pages: 1246-1257
ISSN: 2211-1247 (ISSN-L)
DOI: 10.1016/j.celrep.2015.09.080
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: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
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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Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury

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