Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • 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 ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • 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
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
PKCδ-targeted intervention relieves chronic pain in a murine sickle cell disease model
Ying He, … , Robert E. Molokie, Zaijie Jim Wang
Ying He, … , Robert E. Molokie, Zaijie Jim Wang
Published June 27, 2016
Citation Information: J Clin Invest. 2016;126(8):3053-3057. https://doi.org/10.1172/JCI86165.
View: Text | PDF
Brief Report Hematology

PKCδ-targeted intervention relieves chronic pain in a murine sickle cell disease model

  • Text
  • PDF
Abstract

Pain is a life-long symptom in sickle cell disease (SCD) and a predictor of disease progression and mortality, but little is known about its molecular mechanisms. Here, we characterized pain in a targeted knockin mouse model of SCD (TOW mouse) that exclusively expresses human alleles encoding normal α- and sickle β-globin. TOW mice exhibited ongoing spontaneous pain behavior and increased sensitivity to evoked pain compared with littermate control mice expressing normal human hemoglobins. PKCδ activation was elevated in the superficial laminae of the spinal cord dorsal horn in TOW mice, specifically in GABAergic inhibitory neurons. Functional inhibition and neuron-specific silencing of PKCδ attenuated spontaneous pain, mechanical allodynia, and heat hyperalgesia in TOW mice. Furthermore, we took a hematopoietic stem cell transplantation approach to generating a SCD model in PKCδ-deficient mice. Neither spontaneous pain nor evoked pain was detected in the mice lacking PKCδ despite full establishment of SCD phenotypes. These findings support a critical role of spinal PKCδ in the development of chronic pain in SCD, which may become a potential target for pharmacological interventions.

Authors

Ying He, Diana J. Wilkie, Jonathan Nazari, Rui Wang, Robert O. Messing, Joseph DeSimone, Robert E. Molokie, Zaijie Jim Wang

×

Figure 2

PKCδ inhibition transiently attenuated chronic pain in TOW mice.

Options: View larger image (or click on image) Download as PowerPoint
PKCδ inhibition transiently attenuated chronic pain in TOW mice.
Mechani...
Mechanical (A) and thermal (B) sensitivities before (0) and after the injection of δV1-1 (3 nmole, i.t.). *P < 0.05, ***P < 0.001 vs. 0; ###P<0.001 vs. hβA/hβA. n = 8/group. (C) TOW mice spent significantly more time in δV1-1– than saline-paired chambers, whereas hβA/hβA mice spent similar amounts of time in both chambers. (D) Difference scores confirmed the presence of chamber preference to δV1-1 in TOW but not hβA/hβA mice. *P < 0.05; **P < 0.01. n = 8/group. (E) In TOW mice, plasma membrane translocation of PKCδ (indicated by dashed arrows across representative cells and corresponding fluorescent intensity plots) was abolished 30 minutes after δV1-1 injection. Red, PKCδ; green, NeuN. Scale bars: 20 μm. n = 15 slices from 3 mice. Data were analyzed by ANOVA followed by Dunnett’s t test. Two-way ANOVA (pairing vs. treatment) and post hoc Bonferroni’s test were used to analyze CPP data. Difference scores were analyzed by 2-tailed paired t test.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts