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

被引:37
作者
Ahmed, Aisha S. [1 ]
Berg, Svante [2 ]
Alkass, Kanar [3 ,4 ]
Druid, Henrik [3 ,4 ]
Hart, David A. [5 ]
Svensson, Camilla I. [6 ]
Kosek, Eva [1 ]
机构
[1] Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden
[2] Lowenstromska Hosp, Stockhom Spine Ctr, S-19489 Upplands Vasby, Sweden
[3] Karolinska Inst, Dept Oncol Pathol, S-17177 Stockholm, Sweden
[4] Swedish Natl Board Forens Med, S-17165 Solna, Sweden
[5] Univ Calgary, McCaig Inst Bone & Joint Hlth, Calgary, AB T2N 1N4, Canada
[6] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 03期
基金
瑞典研究理事会;
关键词
nuclear factor-B (NF-B); chronic low back pain; degenerative disc disease (DDD); calcitonin gene related peptide (CGRP); substance P (SP); transient receptor potential V (TRPV); LUMBAR INTERVERTEBRAL DISC; GENE-RELATED PEPTIDE; DORSAL-ROOT GANGLIA; SUBSTANCE-P; RAT MODEL; NEUROPATHIC PAIN; REGULATES PAIN; INHIBITOR; TRPV1; BONE;
D O I
10.3390/ijms20030658
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-B 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-B subunit RelA and NF-B1-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-B1-DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-B1-DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-B1-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-B activation. Moreover, NF-B 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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页数:15
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