Secondary Logo

Institutional members access full text with Ovid®

Share this article on:

Involvement of the VGF-derived peptide TLQP-62 in nerve injury–induced hypersensitivity and spinal neuroplasticity

Skorput, Alexander G. J.a; Zhang, Xijinga; Waataja, Jonathan J.a; Peterson, Cristina D.b; Riedl, Maureen S.a; Kitto, Kelley F.a; Truong, Haia; Huffman, Ceciliaa; Salton, Stephen R.c; Fairbanks, Carolyn A.a,d,e; Honda, Christopher N.a; Vulchanova, Lucya,*

doi: 10.1097/j.pain.0000000000001277
Research Paper

Neuroplasticity in the dorsal horn after peripheral nerve damage contributes critically to the establishment of chronic pain. The neurosecretory protein VGF (nonacronymic) is rapidly and robustly upregulated after nerve injury, and therefore, peptides generated from it are positioned to serve as signals for peripheral damage. The goal of this project was to understand the spinal modulatory effects of the C-terminal VGF-derived peptide TLQP-62 at the cellular level and gain insight into the function of the peptide in the development of neuropathic pain. In a rodent model of neuropathic pain, we demonstrate that endogenous levels of TLQP-62 increased in the spinal cord, and its immunoneutralization led to prolonged attenuation of the development of nerve injury–induced hypersensitivity. Using multiphoton imaging of submaximal glutamate-induced Ca2+ responses in spinal cord slices, we demonstrate the ability of TLQP-62 to potentiate glutamatergic responses in the dorsal horn. We further demonstrate that the peptide selectively potentiates responses of high-threshold spinal neurons to mechanical stimuli in singe-unit in vivo recordings. These findings are consistent with a function of TLQP-62 in spinal plasticity that may contribute to central sensitization after nerve damage.

The study provides evidence for a function of the VGF-derived peptide TLQP-62 in spinal plasticity that may contribute to central sensitization after nerve damage.

aDepartment of Neuroscience, University of Minnesota, Minneapolis, MN, United States

bGraduate Program in Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, United States

cDepartment of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Departments of dPharmacology and

ePharmaceutics, University of Minnesota, Minneapolis, MN, United States

Corresponding author. Address: Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, United States. Tel.: +1 612-626-5726; fax: +1 612-626-9204. E-mail address: vulch001@umn.edu (L. Vulchanova).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received September 06, 2017

Received in revised form April 30, 2018

Accepted May 08, 2018

© 2018 International Association for the Study of Pain
You currently do not have access to this article

To access this article:

Note: If your society membership provides full-access, you may need to login on your society website