title: 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.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, USA Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA Experimental and Clinical Pharmacology Graduate Program, University of Minnesota, Minneapolis, MN, USA Comparative and Molecular Biosciences Graduate Program, University of Minnesota, St. Paul, MN, USA Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, USA.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Fairbanks
authors.forename: Cristina D
authors.initials: CD
authors.lastname: Peterson
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Speltz
authors.forename: Maureen S
authors.initials: MS
authors.lastname: Riedl
authors.forename: Kelley F
authors.initials: KF
authors.lastname: Kitto
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Dykstra
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Braun
authors.forename: Masato
authors.initials: M
authors.lastname: Sadahiro
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Salton
authors.forename: Lucy
authors.initials: L
authors.lastname: Vulchanova
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000506:poisoning; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007278:Injections, Spinal; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051379:Mice; D009414:Nerve Growth Factors; D009437:Neuralgia / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D010543:Peroneal Nerve / Q000293:injuries; D012867:Skin / Q000187:drug effects; D013979:Tibial Nerve / Q000293:injuries; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D009414:Nerve Growth Factors; D009479:Neuropeptides; D010446:Peptide Fragments; C522412:TLQP-21 peptide; C512697:Vgf protein, mouse; D005620:Freund's Adjuvant; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Hyperalgesia; Immunoneutralization; Inflammation; Neuropathic pain; Neuropeptide