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

• Published in: International journal of molecular sciences Vol. 20; no. 3; p. 658
• Main Authors: Ahmed, Aisha S., Berg, Svante, Alkass, Kanar, Druid, Henrik, Hart, David A., Svensson, Camilla I., Kosek, Eva
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.02.2019; MDPI
• Subjects: Adult; Age; Back pain; Body mass index; calcitonin gene related peptide (CGRP); chronic low back pain; Cytokines; Degenerative disc disease; degenerative disc disease (DDD); Deoxyribonucleic acid; DNA; Extracellular matrix; Female; Gender; Gene expression; Gene Expression Regulation; Humans; Intervertebral Disc - metabolism; Intervertebral Disc - physiopathology; Intervertebral Disc Degeneration - complications; Intervertebral Disc Degeneration - genetics; Intervertebral Disc Degeneration - metabolism; Intervertebral Disc Degeneration - physiopathology; Kinases; Male; Middle Aged; Neuropeptides; NF-kappa B - metabolism; NF-kappa B - physiology; NF-kappa B p50 Subunit - metabolism; NF-kappa B p50 Subunit - physiology; nuclear factor-κB (NF-κB); Pain - etiology; Pain - genetics; Pain - metabolism; Proteins; Signal Transduction; substance P (SP); Substance P - genetics; Transcription Factor RelA - metabolism; Transcription Factor RelA - physiology; transient receptor potential V (TRPV); TRPV Cation Channels - genetics; Tumor necrosis factor-TNF; chronic low back pain; substance P (SP); calcitonin gene related peptide (CGRP); degenerative disc disease (DDD); nuclear factor-κB (NF-κB); transient receptor potential V (TRPV)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20030658

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.