EphrinB-EphB signaling regulates spinal pain processing via PKCγ.

Abstract

Spinal ephrinB-EphB signaling is involved in the modulation of pain processing. The aim of the present study was to investigate whether protein kinase C-γ (PKCγ) acts as a downstream effector in regulating spinal pain processing associated with ephrinB-EphB signaling in mice. The intrathecal injection of ephrinB2-Fc, an EphB receptor activator, caused thermal hyperalgesia and mechanical allodynia, as well as increased activation of spinal PKCγ. Knockdown of spinal PKCγ prevented the pain behaviors induced by ephrinB2-Fc. Furthermore, the intrathecal injection of EphB2-Fc, an EphB receptor blocker, suppressed formalin-induced inflammatory, chronic constriction injury (CCI)-induced neuropathic, and tibia bone cavity tumor cell implantation (TCI)-induced bone cancer pain behaviors, in addition to reducing the activation of spinal PKCγ. Finally, the intrathecal injection of MK801, an N-methyl-D-aspartate (NMDA) receptor blocker, prevented the pain behaviors and spinal PKCγ activation induced by ephrinB2-Fc. Overall, the results confirm the important role of PKCγ in the regulation of spinal pain processing associated with ephrinB-EphB signaling.

• Authors: X-L Zhou, C-J Zhang, Y Wang, M Wang, L-H Sun, L-N Yu, J-L Cao, M Yan
• Journal: Neuroscience (Neuroscience) Vol. 307 Pg. 64-72 (Oct 29 2015) ISSN: 1873-7544 [Electronic] United States
• PMID: 26318332 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Ephrin-B2
• RNA, Small Interfering
• Formaldehyde
• protein kinase C gamma
• Receptors, Eph Family
• Protein Kinase C

Topics

• Analysis of Variance
• Animals
• Bone Neoplasms (complications)
• Disease Models, Animal
• Ephrin-B2 (chemistry, metabolism, toxicity)
• Formaldehyde (toxicity)
• Hyperalgesia (physiopathology)
• Injections, Spinal
• Male
• Mice
• Mice, Inbred C57BL
• Neuralgia (chemically induced, etiology, metabolism)
• Protein Kinase C (genetics, metabolism)
• RNA, Small Interfering (pharmacology)
• Receptors, Eph Family (metabolism, toxicity)
• Signal Transduction (drug effects, physiology)
• Time Factors