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.

Fexofenadine Protects Against Intervertebral Disc Degeneration Through TNF Signaling

“…Intervertebral disc-derived low back pain is a common cause of low back pain, with the aging of the population, the incidence is gradually increasing ( GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2018 ; Hartvigsen et al, 2018 ). IVD degeneration is a basic cause of low back pain and a common degenerative disease ( Lyu et al, 2021 ). Unfortunately, there are currently no drugs to block the progression of IVD degeneration ( Cheng et al, 2018 ), and end-stage patients have to undergo surgical treatment, but surgical treatment can aggravate the degeneration of adjacent segments of the spine and bring new problems ( Okuda et al, 2018 ).…”

“…In the process of IVD degeneration, the expression of pro-inflammatory cytokines in IVD cells increases and leads to the degradation of the ECM, which leads to changes in the structure and biomechanics of the IVD. At the same time, the inflammatory response mediated by immune cells was enhanced in the degenerated IVD, which led to the decrease of the number of NP cells and the deterioration of the IVD microenvironment ( Zhao et al, 2020 ; Lyu et al, 2021 ). TNF-α is at the top of the inflammatory cascade and plays an important role in the progression of IVD degeneration ( Croft et al, 2013 ; Wei et al, 2020a ).…”

Roles of circular RNAs in the pathogenesis of intervertebral disc degeneration (Review)

“…Inflammatory mediators and signaling pathways are recognized as major contributors to the onset and development of IDD. Elevated levels of inflammatory molecules have been detected in IDD tissues compared with those in healthy controls ( 45 ). Furthermore, ICs, particularly TNF-α and IL-1β, have been demonstrated to stimulate and deteriorate the progression of IDD ( 46 ).…”

Stem Cell Therapy and Exercise for Treatment of Intervertebral Disc Degeneration

“…The level of cytokines and proinflammatory mediators including IL-1 α , IL-1 β , IL-6, and IL-7 increases. The infiltration of immune cells is intensified [ 21 ]. Abundant macrophage and mast cell infiltration were observed in patients with LBP.…”