Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia
Yan Lu, … , Ru-Rong Ji, Lize Xiong
Yan Lu, … , Ru-Rong Ji, Lize Xiong
Published August 27, 2013
Citation Information: J Clin Invest. 2013;123(9):4050-4062. https://doi.org/10.1172/JCI70026.
View: Text | PDF
Research Article Neuroscience

A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia

  • Text
  • PDF
Abstract

Neuropathic pain is characterized by mechanical allodynia induced by low-threshold myelinated Aβ-fiber activation. The original gate theory of pain proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn (DH) act as “gate control” units for preventing the interaction between innocuous and nociceptive signals. However, our understanding of the neuronal circuits underlying pain signaling and modulation in the spinal DH is incomplete. Using a rat model, we have shown that the convergence of glycinergic inhibitory and excitatory Aβ-fiber inputs onto PKCγ+ neurons in the superficial DH forms a feed-forward inhibitory circuit that prevents Aβ input from activating the nociceptive pathway. This feed-forward inhibition was suppressed following peripheral nerve injury or glycine blockage, leading to inappropriate induction of action potential outputs in the nociceptive pathway by Aβ-fiber stimulation. Furthermore, spinal blockage of glycinergic synaptic transmission in vivo induced marked mechanical allodynia. Our findings identify a glycinergic feed-forward inhibitory circuit that functions as a gate control to separate the innocuous mechanoreceptive pathway and the nociceptive pathway in the spinal DH. Disruption of this glycinergic inhibitory circuit after peripheral nerve injury has the potential to elicit mechanical allodynia, a cardinal symptom of neuropathic pain.

Authors

Yan Lu, Hailong Dong, Yandong Gao, Yuanyuan Gong, Yingna Ren, Nan Gu, Shudi Zhou, Nan Xia, Yan-Yan Sun, Ru-Rong Ji, Lize Xiong

×

Figure 7

Blockage or activation of spinal Gly synaptic transmission differentially regulates mechanical allodynia.

Options: View larger image (or click on image) Download as PowerPoint
Blockage or activation of spinal Gly synaptic transmission differentiall...
(A and B) SNL induced (A and C) mechanical allodynia and (B and D) thermal hyperalgesia manifested as a lowered threshold of mechanical or thermal withdrawal in rats. Ten rats were included in each group. (C and D) The SNL-induced mechanical allodynia was attenuated by intrathecal glycine, and this effect was blocked by strychnine. The same dose of glycine had no effect on the SNL-induced thermal hyperalgesia. Six rats were included in each group. (E and F) Intrathecal injection of strychnine induced robust mechanical allodynia but mild thermal hyperalgesia in naive rats. Six rats were included in each group. (*P < 0.05, **P < 0.01, compared with vehicle or sham controls, 1-way ANOVA with Bonferroni post-hoc test).

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts