The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity.

Abstract

VGF (nonacronymic) is a granin-like protein that is packaged and proteolytically processed within the regulated secretory pathway. VGF and peptides derived from its processing have been implicated in neuroplasticity associated with learning, memory, depression, and chronic pain. In sensory neurons, VGF is rapidly increased following peripheral nerve injury and inflammation. Several bioactive peptides generated from the C-terminus of VGF have pronociceptive spinal effects. The goal of the present study was to examine the spinal effects of the peptide TLQP-21 and determine whether it participates in spinal mechanisms of persistent pain. Application of exogenous TLQP-21 induced dose-dependent thermal hyperalgesia in the warm-water immersion tail-withdrawal test. This hyperalgesia was inhibited by a p38 mitogen-activated protein kinase inhibitor, as well as inhibitors of cyclooxygenase and lipoxygenase. We used immunoneutralization of TLQP-21 to determine the function of the endogenous peptide in mechanisms underlying persistent pain. In mice injected intradermally with complete Freund adjuvant, intrathecal treatment with anti-TLQP-21 immediately prior to or 5hours after induction of inflammation dose-dependently inhibited tactile hypersensitivity and thermal hyperalgesia. Intrathecal anti-TL21 administration also attenuated the development and maintenance of tactile hypersensitivity in the spared nerve injury model of neuropathic pain. These results provide evidence that endogenous TLQP-21 peptide contributes to the mechanisms of spinal neuroplasticity after inflammation and nerve injury.

• Authors: Carolyn A Fairbanks, Cristina D Peterson, Rebecca H Speltz, Maureen S Riedl, Kelley F Kitto, Jaclyn A Dykstra, Patrick D Braun, Masato Sadahiro, Stephen R Salton, Lucy Vulchanova
• Journal: Pain (Pain) Vol. 155 Issue 7 Pg. 1229-1237 (Jul 2014) ISSN: 1872-6623 [Electronic] United States
• PMID: 24657450 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chemical References

• Cyclooxygenase Inhibitors
• Lipoxygenase Inhibitors
• Nerve Growth Factors
• Neuropeptides
• Peptide Fragments
• TLQP-21 peptide
• Vgf protein, mouse
• Freund's Adjuvant
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Cyclooxygenase Inhibitors (pharmacology)
• Disease Models, Animal
• Freund's Adjuvant (poisoning)
• Hot Temperature
• Hyperalgesia (chemically induced, metabolism)
• Inflammation (chemically induced, metabolism)
• Injections, Spinal
• Lipoxygenase Inhibitors (pharmacology)
• Mice
• Nerve Growth Factors
• Neuralgia (metabolism)
• Neuropeptides (metabolism)
• Nociception (drug effects, physiology)
• Peptide Fragments (metabolism, pharmacology)
• Peripheral Nerve Injuries (metabolism)
• Peroneal Nerve (injuries)
• Skin (drug effects)
• Tibial Nerve (injuries)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)