Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions

Abstract

Low back pain (LBP), as a leading cause of disability, is a common musculoskeletal disorder that results in major social and economic burdens. Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration, a significant contributor to LBP. Inflammatory mediators also play an indispensable role in discogenic LBP. The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies. Here, an overview of the advances in inflammation-related pain in disc degeneration is provided, with a discussion on the role of inflammation in IVD degeneration and pain induction. Puncture models, mechanical models, and spontaneous models as the main animal models to study painful disc degeneration are discussed, and the underlying signaling pathways are summarized. Furthermore, potential drug candidates, either under laboratory investigation or undergoing clinical trials, to suppress discogenic LBP by eliminating inflammation are explored. We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.

Fig. 1

Illustration of degenerative changes in painful intervertebral discs. During IVD degeneration, proteoglycans and collagen II are decreased, while collagen I and III are increased in the extracellular matrix. Emerging cytokines, chemokines, and pain-related factors synergistically contribute to discogenic pain development. IVD intervertebral disc, NP nucleus pulposus, AF annulus fibrosus

Fig. 2

Animal models of painful IVD degeneration. These models include a mechanical model, a needle puncture model through a posterior or anterior approach, and a spontaneous IVD degeneration and LBP model represented by SPARC-null mice. IVD intervertebral disc, LBP low back pain, SPARC secreted protein acidic and rich in cysteine

Fig. 3

Signaling pathways involved in intervertebral disc degeneration and pain. These pathways include NF-κB signaling, MAPK signaling, and TLR signaling. NF-κB nuclear factor kappa-B, MAPK mitogen-activated protein kinase, TLR Toll-like receptor. IL interleukin, TRPV1 transient receptor potential cation channel subfamily V member 1, PG prostaglandins, TGF-β1 transforming growth factor β1, ERK extracellular signal-regulated kinases, CCL chemokine (C-C motif) ligand, PAMP pathogen-associated molecular patterns, NGF nerve growth factor, BDNF brain-derived neurotrophic factor, CXCL chemokine (C-X-C motif) ligand

Fig. 4

Molecules under laboratory investigation to target inflammation and discogenic pain. IVD intervertebral disc, TNF-α tumor necrosis factor α, LMP-1 LIM mineralization protein-1, SHOX2 short stature homeobox 2, TGF-β transforming growth factor β, GDF growth and differentiation factor, IL-1Ra IL-1 receptor antagonist