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

Alexander G.J. Skorput, Xijing Zhang, Jonathan J. Waataja, Cristina D. Peterson, Maureen S Riedl, Kelley F Kitto, Hai Truong, Cecilia Huffman, Stephen R. Salton, Carolyn A Fairbanks, Christopher N. Honda, Lucy Vulchanova

Research output: Contribution to journalArticle

Abstract

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 Ca 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.

Original languageEnglish (US)
Pages (from-to)1802-1813
Number of pages12
JournalPain
Volume159
Issue number9
DOIs
StatePublished - Sep 1 2018

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Neuronal Plasticity
Hypersensitivity
Neuralgia
Peptides
Spinal Cord
Wounds and Injuries
Central Nervous System Sensitization
Peripheral Nerves
Chronic Pain
Glutamic Acid
Rodentia
Neurons
VGF peptide
Proteins
Spinal Cord Dorsal Horn

PubMed: MeSH publication types

  • Journal Article

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Involvement of the VGF-derived peptide TLQP-62 in nerve injury-induced hypersensitivity and spinal neuroplasticity. / Skorput, Alexander G.J.; Zhang, Xijing; Waataja, Jonathan J.; Peterson, Cristina D.; Riedl, Maureen S; Kitto, Kelley F; Truong, Hai; Huffman, Cecilia; Salton, Stephen R.; Fairbanks, Carolyn A; Honda, Christopher N.; Vulchanova, Lucy.

In: Pain, Vol. 159, No. 9, 01.09.2018, p. 1802-1813.

Research output: Contribution to journalArticle

Skorput, Alexander G.J. ; Zhang, Xijing ; Waataja, Jonathan J. ; Peterson, Cristina D. ; Riedl, Maureen S ; Kitto, Kelley F ; Truong, Hai ; Huffman, Cecilia ; Salton, Stephen R. ; Fairbanks, Carolyn A ; Honda, Christopher N. ; Vulchanova, Lucy. / Involvement of the VGF-derived peptide TLQP-62 in nerve injury-induced hypersensitivity and spinal neuroplasticity. In: Pain. 2018 ; Vol. 159, No. 9. pp. 1802-1813.
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