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: firstname.lastname@example.org (L. Vulchanova).
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Received September 06, 2017
Received in revised form April 30, 2018
Accepted May 08, 2018