Cargando…

Involvement of CX3CL1/CX3CR1 Signaling in Spinal Long Term Potentiation

The long-term potentiation (LTP) of spinal C-fiber-evoked field potentials is considered as a fundamental mechanism of central sensitization in the spinal cord. Accumulating evidence has showed the contribution of spinal microglia to spinal LTP and pathological pain. As a key signaling of neurons-mi...

Descripción completa

Detalles Bibliográficos
Autores principales: Bian, Chao, Zhao, Zhi-Qi, Zhang, Yu-Qiu, Lü, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358970/
https://www.ncbi.nlm.nih.gov/pubmed/25768734
http://dx.doi.org/10.1371/journal.pone.0118842
_version_ 1782361319964409856
author Bian, Chao
Zhao, Zhi-Qi
Zhang, Yu-Qiu
Lü, Ning
author_facet Bian, Chao
Zhao, Zhi-Qi
Zhang, Yu-Qiu
Lü, Ning
author_sort Bian, Chao
collection PubMed
description The long-term potentiation (LTP) of spinal C-fiber-evoked field potentials is considered as a fundamental mechanism of central sensitization in the spinal cord. Accumulating evidence has showed the contribution of spinal microglia to spinal LTP and pathological pain. As a key signaling of neurons-microglia interactions, the involvement of CX3CL1/CX3CR1 signaling in pathological pain has also been investigated extensively. The present study examined whether CX3CL1/CX3CR1 signaling plays a role in spinal LTP. The results showed that 10-trains tetanic stimulation (100 Hz, 2s) of the sciatic nerve (TSS) produced a significant LTP of C-fiber-evoked field potentials lasting for over 3 h in the rat spinal dorsal horn. Blockade of CX3CL1/CX3CR1 signaling with an anti-CX3CR1 neutralizing antibody (CX3CR1 AB) markedly suppressed TSS-induced LTP. Exogenous CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats. Consistently, spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz, 1s, 4 trains) in all C57BL/6 wild type (WT) mice. However, in CX3CR1(-/-) mice, TSS failed to induce LTP and behavioral hypersensitivity, confirming an essential role of CX3CR1 in spinal LTP induction. Furthermore, blockade of IL-18 or IL-23, the potential downstream factors of CX3CL1/CX3CR1 signaling, with IL-18 BP or anti-IL-23 neutralizing antibody (IL-23 AB), obviously suppressed spinal LTP in rats. These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C-fiber-evoked field potentials in the rodent spinal dorsal horn.
format Online
Article
Text
id pubmed-4358970
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-43589702015-03-23 Involvement of CX3CL1/CX3CR1 Signaling in Spinal Long Term Potentiation Bian, Chao Zhao, Zhi-Qi Zhang, Yu-Qiu Lü, Ning PLoS One Research Article The long-term potentiation (LTP) of spinal C-fiber-evoked field potentials is considered as a fundamental mechanism of central sensitization in the spinal cord. Accumulating evidence has showed the contribution of spinal microglia to spinal LTP and pathological pain. As a key signaling of neurons-microglia interactions, the involvement of CX3CL1/CX3CR1 signaling in pathological pain has also been investigated extensively. The present study examined whether CX3CL1/CX3CR1 signaling plays a role in spinal LTP. The results showed that 10-trains tetanic stimulation (100 Hz, 2s) of the sciatic nerve (TSS) produced a significant LTP of C-fiber-evoked field potentials lasting for over 3 h in the rat spinal dorsal horn. Blockade of CX3CL1/CX3CR1 signaling with an anti-CX3CR1 neutralizing antibody (CX3CR1 AB) markedly suppressed TSS-induced LTP. Exogenous CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats. Consistently, spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz, 1s, 4 trains) in all C57BL/6 wild type (WT) mice. However, in CX3CR1(-/-) mice, TSS failed to induce LTP and behavioral hypersensitivity, confirming an essential role of CX3CR1 in spinal LTP induction. Furthermore, blockade of IL-18 or IL-23, the potential downstream factors of CX3CL1/CX3CR1 signaling, with IL-18 BP or anti-IL-23 neutralizing antibody (IL-23 AB), obviously suppressed spinal LTP in rats. These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C-fiber-evoked field potentials in the rodent spinal dorsal horn. Public Library of Science 2015-03-13 /pmc/articles/PMC4358970/ /pubmed/25768734 http://dx.doi.org/10.1371/journal.pone.0118842 Text en © 2015 Bian et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bian, Chao
Zhao, Zhi-Qi
Zhang, Yu-Qiu
Lü, Ning
Involvement of CX3CL1/CX3CR1 Signaling in Spinal Long Term Potentiation
title Involvement of CX3CL1/CX3CR1 Signaling in Spinal Long Term Potentiation
title_full Involvement of CX3CL1/CX3CR1 Signaling in Spinal Long Term Potentiation
title_fullStr Involvement of CX3CL1/CX3CR1 Signaling in Spinal Long Term Potentiation
title_full_unstemmed Involvement of CX3CL1/CX3CR1 Signaling in Spinal Long Term Potentiation
title_short Involvement of CX3CL1/CX3CR1 Signaling in Spinal Long Term Potentiation
title_sort involvement of cx3cl1/cx3cr1 signaling in spinal long term potentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358970/
https://www.ncbi.nlm.nih.gov/pubmed/25768734
http://dx.doi.org/10.1371/journal.pone.0118842
work_keys_str_mv AT bianchao involvementofcx3cl1cx3cr1signalinginspinallongtermpotentiation
AT zhaozhiqi involvementofcx3cl1cx3cr1signalinginspinallongtermpotentiation
AT zhangyuqiu involvementofcx3cl1cx3cr1signalinginspinallongtermpotentiation
AT luning involvementofcx3cl1cx3cr1signalinginspinallongtermpotentiation