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Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury

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Peirs, Cedric, Williams, Sean-Paul G., Zhao, Xinyi, Arokiaraj, Cynthia M., Ferreira, David W., Noh, Myung-chul, Smith, Kelly M., Halder, Priyabrata, Corrigan, Kelly A., Gedeon, Jeremy Y., Lee, Suh Jin, Gatto, Graziana, Chi, David, Ross, Sarah E., Goulding, Martyn, Seal, Rebecca P.·2021·Neuron

DOI 10.1016/j.neuron.2020.10.027PMC PMC7806207

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Abstract

The spinal dorsal horn is a major site for the induction and maintenance of mechanical allodynia, but the circuitry that underlies this clinically important form of pain remains unclear. The studies presented here provide strong evidence that the neural circuits conveying mechanical allodynia in the dorsal horn differ by the nature of the injury. Calretinin (CR) neurons in lamina II inner convey mechanical allodynia induced by inflammatory injuries, while protein kinase C gamma (PKCγ) neurons at the lamina II/III border convey mechanical allodynia induced by neuropathic injuries. Cholecystokinin (CCK) neurons located deeper within the dorsal horn (laminae III-IV) are important for both types of injuries. Interestingly, the Maf+ subset of CCK neurons is composed of transient vesicular glutamate transporter 3 (tVGLUT3) neurons, which convey primarily dynamic allodynia. Identification of an etiology-based circuitry for mechanical allodynia in the dorsal horn has important implications for the mechanistic and clinical understanding of this condition.

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Authors: Peirs, C., Williams, S.-P. G., Zhao, X., Arokiaraj, C. M., Ferreira, D. W., Noh, M.-C., Smith, K. M., Halder, P., Corrigan, K. A., Gedeon, J. Y., Lee, S. J., Gatto, G., Chi, D., Ross, S. E., Goulding, M., & Seal, R. P.
Affiliations: University of Pittsburgh (US)
Salk Institute for Biological Studies (US)
Corresponding author: Seal, Rebecca P.
ORCID: Peirs, Cedric
Williams, Sean-Paul G.
Zhao, Xinyi
Arokiaraj, Cynthia M.
Ferreira, David W.
Noh, Myung-chul
Smith, Kelly M.
Halder, Priyabrata
Gedeon, Jeremy Y.
Gatto, Graziana
Ross, Sarah E.
Goulding, Martyn
Seal, Rebecca P.
Venue: Neuron
Publisher: Elsevier BV
Published: 2021-01
Volume: 109
Issue: 1
Pages: 73-90.e7
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2020.10.027
PMC: PMC7806207
OpenAlex: W3100514562
Cited by: 190
References: 64
Citations by year: 2026: 26 · 2025: 26 · 2024: 42 · 2023: 35 · 2022: 38 · 2021: 21
FWCI: 14.43
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
HAL (submittedVersion)
Funders: National Institutes of Health
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: mechanical allodynia, dorsal horn, central sensitization, VGLUT3, injury etiology, nociception
MeSH terms: Animals, Female, Hyperalgesia, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Pain Measurement, Spinal Cord Injuries, Amino Acid Transport Systems, Acidic, Mice, Spinal Cord Dorsal Horn

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Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury

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