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

Area of Science:

• Biochemistry
• Neuroscience
• Pain Research

Background:

• Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways are implicated in inflammatory and neuropathic pain.
• Chronic back pain associated with degenerative disc disease (DDD) involves complex biological mechanisms.
• Understanding the role of NF-κB in pain neuropeptide expression in DDD is crucial for targeted therapies.

Purpose of the Study:

• To investigate the association between NF-κB signaling and pain-related neuropeptide expression in patients with DDD.
• To determine if NF-κB activation correlates with specific gene and protein markers of pain in intervertebral disc (IVD) tissues.

Main Methods:

• Collected intervertebral disc (IVD) tissues from DDD patients and postmortem controls.
• Analyzed gene expression of RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 using RT-qPCR.
• Assessed protein levels of NF-κB subunits (RelA, NF-κB1), CGRP, substance P (SP), and TRPV1 using ELISA.

Main Results:

• Elevated NF-κB1 DNA binding and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to controls.
• NF-κB1 DNA binding positively correlated with nuclear RelA levels in DDD patients.
• NF-κB1 DNA binding was associated with TRPV1 and MMP-3 gene expression, and SP and TRPV1 protein levels in DDD patients.

Conclusions:

• NF-κB activation is associated with the expression of substance P (SP) and TRPV1 in the intervertebral disc (IVD) tissues of DDD patients.
• NF-κB signaling may play a role in the generation or maintenance of peripheral pain mechanisms in DDD through the regulation of pain neuropeptides.