Dorsal Horn Circuits for Persistent Mechanical Pain

Peirs, Cedric; Williams, Sean-Paul G.; Zhao, Xinyi; Walsh, Claire E.; Gedeon, Jeremy Y.; Cagle, Natalie E.; Goldring, Adam C.; Hioki, Hiroyuki; Liu, Zheng; Marell, Paulina S.; Seal, Rebecca P.

doi:10.1016/j.neuron.2015.07.029

Cited by 327Pain Mechanisms and TreatmentsPain Management and TreatmentIon Channels and Receptors

Dorsal Horn Circuits for Persistent Mechanical Pain

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Peirs, Cedric, Williams, Sean-Paul G., Zhao, Xinyi, Walsh, Claire E., Gedeon, Jeremy Y., Cagle, Natalie E., Goldring, Adam C., Hioki, Hiroyuki +3 more·2015·Neuron

DOI 10.1016/j.neuron.2015.07.029PMC PMC4562334

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Abstract

Persistent mechanical hypersensitivity that occurs in the setting of injury or disease remains a major clinical problem largely because the underlying neural circuitry is still not known. Here we report the functional identification of key components of the elusive dorsal horn circuit for mechanical allodynia. We show that the transient expression of VGLUT3 by a discrete population of neurons in the deep dorsal horn is required for mechanical pain and that activation of the cells in the adult conveys mechanical hypersensitivity. The cells, which receive direct low threshold input, point to a novel location for circuit initiation. Subsequent analysis of c-Fos reveals the circuit extends dorsally to nociceptive lamina I projection neurons, and includes lamina II calretinin neurons, which we show also convey mechanical allodynia. Lastly, using inflammatory and neuropathic pain models, we show that multiple microcircuits in the dorsal horn encode this form of pain.

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The Maf dorsal excitatory family comprised Excit-5, Excit-6, and Excit-7, which expressed markers of neurons involved in light touch.
“The Maf dorsal, the excitatory family was comprised of Excit-5, Excit-6, and Excit-7 which expressed markers of neurons involved in light touch46,48,50,56,57.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [56]
The Prkcg dorsal excitatory family comprised Excit-3 and Excit-4 and likely corresponded to neurons involved in light static touch and allodynic pain in pathological situations.
“The Prkcg dorsal, excitatory family was comprised of Excit-3 and Excit-4 and likely corresponded to neurons involved in light static touch and allodynic pain in pathological situations46,48–56.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [56]
The Sox5 dorsal excitatory family comprised Excit-14, Excit-15, Excit-16, Excit-17, Excit-18, and Excit-19 and expressed markers suggestive of a role in coping pain and mechanical nociception.
“The Sox5 dorsal, the excitatory family was comprised of Excit-14, Excit-15, Excit-16, Excit-17, Excit-18, and Excit-19, and expressed markers suggestive of a role in coping pain and mechanical nociception46,52,56,63–67.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [56]

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Authors: Peirs, C., Williams, S.-P. G., Zhao, X., Walsh, C. E., Gedeon, J. Y., Cagle, N. E., Goldring, A. C., Hioki, H., Liu, Z., Marell, P. S., & Seal, R. P.
Affiliations: University of Pittsburgh (US)
Kyoto University (JP)
Corresponding author: Seal, Rebecca P.
ORCID: Williams, Sean-Paul G.
Zhao, Xinyi
Gedeon, Jeremy Y.
Goldring, Adam C.
Hioki, Hiroyuki
Liu, Zheng
Marell, Paulina S.
Seal, Rebecca P.
Venue: Neuron
Publisher: Elsevier BV
Published: 2015-08
Volume: 87
Issue: 4
Pages: 797-812
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2015.07.029
PMC: PMC4562334
OpenAlex: W2169382112
Cited by: 327
References: 51
Citations by year: 2026: 19 · 2025: 17 · 2024: 21 · 2023: 30 · 2022: 34 · 2021: 34 · 2020: 40 · 2019: 36 · 2018: 36 · 2017: 34 · 2016: 22 · 2015: 3
FWCI: 23.33
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
HAL (submittedVersion, cc-by)
Funders: National Institutes of Health (UL1TR000005)
Japan Society for the Promotion of Science (15K14333, 15H01430)
National Institute of Neurological Disorders and Stroke (NS084191, T32NS007433, R21NS084191)
National Center for Advancing Translational Sciences
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: dorsal horn, mechanical allodynia, mechanical hypersensitivity, VGLUT3, glutamate uptake, lamina II, nociceptive circuits, neuropathic pain, inflammatory pain, chronic pain
MeSH terms: Animals, Hyperalgesia, Nerve Net, Organ Culture Techniques, Pain, Touch, Mice, Knockout, Amino Acid Transport Systems, Acidic, Mice, Spinal Cord Dorsal Horn

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Dorsal Horn Circuits for Persistent Mechanical Pain

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