Research article summary (published 19 Oct 2009):

Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in nociceptive processing.

Full Abstract

Peripheral tissue injury is associated with changes in protein expression in sensory neurons that may contribute to abnormal nociceptive processing. We used cultured dorsal root ganglion (DRG) neurons as a model of axotomized neurons to investigate early changes in protein expression after nerve injury. Comparing protein levels immediately after DRG dissociation and 24 h later by proteomic differential expression analysis, we found a substantial increase in the levels of the neurotrophin-inducible protein VGF (nonacronymic), a putative neuropeptide precursor. In a rodent model of nerve injury, VGF levels were increased within 24 h in both injured and uninjured DRG neurons, and the increase persisted for at least 7 d. VGF was also upregulated 24 h after hindpaw inflammation. To determine whether peptides derived from proteolytic processing of VGF participate in nociceptive signaling, we examined the spinal effects of AQEE-30 and LQEQ-19, potential proteolytic products shown previously to be bioactive. Each peptide evoked dose-dependent thermal hyperalgesia that required activation of the mitogen-activated protein kinase p38. In addition, LQEQ-19 induced p38 phosphorylation in spinal microglia when injected intrathecally and in the BV-2 microglial cell line when applied in vitro. In summary, our results demonstrate rapid upregulation of VGF in sensory neurons after nerve injury and inflammation and activation of microglial p38 by VGF peptides. Therefore, VGF peptides released from sensory neurons may participate in activation of spinal microglia after peripheral tissue injury.

Author information

Author/s: Riedl, Maureen S (MS); Braun, Patrick D (PD); Kitto, Kelley F (KF); Roiko, Samuel A (SA); Anderson, Lorraine B (LB); Honda, Christopher N (CN); Fairbanks, Carolyn A (CA); Vulchanova, Lucy (L);

Affiliation: Departments of Neuroscience, Pharmaceutics, Pharmacology, and Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.

Grants: K01 DA017236 (Agency:NIDA NIH HHS) ; T32 DA07234 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 42) : pp 13377-88

Dates: Created 2009/10/22; Completed 2009/11/06;

PMID: 19846725, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Benzoxazoles - metabolism Cells, Cultured Disease Models, Animal Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology Freund's Adjuvant Ganglia, Spinal - drug effects; metabolism; pathology Hyperalgesia - chemically induced; metabolism Imidazoles - pharmacology Inflammation - chemically induced; metabolism Male Microglia - drug effects; metabolism Neurons, Afferent - metabolism Neuropeptides - chemistry; metabolism; pharmacology Nociceptors - physiology

Organ Culture Techniques Pain Measurement - drug effects Peptides - pharmacology Peripheral Nervous System Diseases - etiology; metabolism; pathology Proteomics Pyridines - pharmacology Quinolinium Compounds - metabolism Rats Rats, Sprague-Dawley Reaction Time - drug effects Receptor, trkA - metabolism Receptors, Purinergic P2 - metabolism Signal Transduction - drug effects Spinal Cord Injuries - metabolism Time Factors Up-Regulation - drug effects; physiology

Associated Chemicals: 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole (0) ; Benzoxazoles (0) ; Enzyme Inhibitors (0) ; Imidazoles (0) ; Neuropeptides (0) ; Peptides (0) ; Pyridines (0) ; Quinolinium Compounds (0) ; Receptors, Purinergic P2 (0) ; VGF peptide (0) ; Vgf protein, rat (0) ; purinoceptor P2X3 (0) ; 1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium (143413-85-8) ; Freund's Adjuvant (9007-81-2) ; Receptor, trkA (EC 2.7.1.112)

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