Involvement of the VGF-derived peptide TLQP-62 in nerve injury-induced hypersensitivity and spinal neuroplasticity
| Autor: | Christopher N. Honda, Xijing Zhang, Lucy Vulchanova, Kelley F. Kitto, Maureen S. Riedl, Stephen R.J. Salton, Carolyn A. Fairbanks, Alexander G. J. Skorput, Jonathan J. Waataja, Hai Truong, Cecilia Huffman, Cristina D. Peterson |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Article Rats Sprague-Dawley 03 medical and health sciences Glutamatergic Mice 0302 clinical medicine Downregulation and upregulation In vivo Peripheral Nerve Injuries Neuroplasticity medicine Animals Pain Measurement Neurons Neuronal Plasticity business.industry Neuropeptides Chronic pain Nerve injury Spinal cord medicine.disease Rats 030104 developmental biology Anesthesiology and Pain Medicine medicine.anatomical_structure Neurology Spinal Cord Hyperalgesia Neuropathic pain Calcium Neurology (clinical) medicine.symptom business Peptides Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Pain. 159(9) |
| ISSN: | 1872-6623 |
| Popis: | Neuroplasticity in the dorsal horn following peripheral nerve damage contributes critically to the establishment of chronic pain. The neurosecretory protein VGF (non-acronymic) is rapidly and robustly upregulated following 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 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(2+) 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 following nerve damage. |
| Databáze: | OpenAIRE |
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