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NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease

The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression...

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Autores principales: Ahmed, Aisha S., Berg, Svante, Alkass, Kanar, Druid, Henrik, Hart, David A., Svensson, Camilla I., Kosek, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386867/
https://www.ncbi.nlm.nih.gov/pubmed/30717434
http://dx.doi.org/10.3390/ijms20030658
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author Ahmed, Aisha S.
Berg, Svante
Alkass, Kanar
Druid, Henrik
Hart, David A.
Svensson, Camilla I.
Kosek, Eva
author_facet Ahmed, Aisha S.
Berg, Svante
Alkass, Kanar
Druid, Henrik
Hart, David A.
Svensson, Camilla I.
Kosek, Eva
author_sort Ahmed, Aisha S.
collection PubMed
description The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects. RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 gene expression were analyzed by RT-qPCR, while NF-κB subunit RelA and NF-κB1–DNA binding in nuclear extracts and calcitonin gene related peptide (CGRP), substance P (SP), and transient receptor potential, subfamily V, member 1 (TRPV1) protein levels in cytosolic extracts of tissues were assessed by enzyme-linked immunosorbent assay (ELISA). An upregulated NF-κB1–DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-κB1–DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-κB1–DNA binding was positively associated with TRPV1 and MMP-3 gene and SP and TRPV1 protein expression in DDD patients. Our results indicate that the expression of SP and TRPV1 in IVD tissues was associated with NF-κB activation. Moreover, NF-κB may be involved in the generation or maintenance of peripheral pain mechanisms by the regulation of pain-related neuropeptide expression in DDD patients.
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spelling pubmed-63868672019-02-27 NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease Ahmed, Aisha S. Berg, Svante Alkass, Kanar Druid, Henrik Hart, David A. Svensson, Camilla I. Kosek, Eva Int J Mol Sci Article The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects. RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 gene expression were analyzed by RT-qPCR, while NF-κB subunit RelA and NF-κB1–DNA binding in nuclear extracts and calcitonin gene related peptide (CGRP), substance P (SP), and transient receptor potential, subfamily V, member 1 (TRPV1) protein levels in cytosolic extracts of tissues were assessed by enzyme-linked immunosorbent assay (ELISA). An upregulated NF-κB1–DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-κB1–DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-κB1–DNA binding was positively associated with TRPV1 and MMP-3 gene and SP and TRPV1 protein expression in DDD patients. Our results indicate that the expression of SP and TRPV1 in IVD tissues was associated with NF-κB activation. Moreover, NF-κB may be involved in the generation or maintenance of peripheral pain mechanisms by the regulation of pain-related neuropeptide expression in DDD patients. MDPI 2019-02-03 /pmc/articles/PMC6386867/ /pubmed/30717434 http://dx.doi.org/10.3390/ijms20030658 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahmed, Aisha S.
Berg, Svante
Alkass, Kanar
Druid, Henrik
Hart, David A.
Svensson, Camilla I.
Kosek, Eva
NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease
title NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease
title_full NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease
title_fullStr NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease
title_full_unstemmed NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease
title_short NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease
title_sort nf-κb-associated pain-related neuropeptide expression in patients with degenerative disc disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386867/
https://www.ncbi.nlm.nih.gov/pubmed/30717434
http://dx.doi.org/10.3390/ijms20030658
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