The role of structure and function changes of sensory nervous system in intervertebral disc-related low back pain

Zhang, S.; Hu, Binwu; Liu, W.; Wang, P.; Lv, Xiao; Chen, S.; Shao, Zengwu

doi:10.1016/j.joca.2020.09.002

Cited by 58 publications

(52 citation statements)

References 129 publications

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“…The normal structure of IVD is avascular that is poorly innervated, with the most nerve fibers existing in the outer 1/3 of AF [ 12 ]. In the past few decades, the role and changes of nerve systems during the progression of IVDD have attracted growing attention among researches [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

Sun

Zhu

Chang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Chronic low back pain (CLBP) has been proved to be the dominating cause of disability in patients with lumbar degenerative diseases. Of the various etiological factors, intervertebral disc degeneration (IVDD) has been the dominating cause. In the past few decades, the role and changes of nerve systems, especially the peripheral sensory fibers and their neurotransmitters, in the induction and progression of IVDD have attracted growing concerns. The expression of many neuropeptides, such as SP, NPY, and CGRP, in the nociceptive pathways is increased during the progression of IVDD and responsible for the discogenic pain. Here, the role of CGRP in the progression of IVDD was firstly investigated both in vitro and in vivo. Firstly, we confirmed that human degenerated intervertebral disc tissue exhibited elevated expression of CGRP and its receptor. Secondly, in vitro experiments suggested that CGRP could inhibit the proliferation and induce apoptosis in human nucleus pulposus (NP) cells, as well as promote inflammation and degenerated phenotypes through activating NF-κB and MAPK signaling pathways. Thirdly, CGRP receptor antagonist, Rimegepant, can ameliorate the adverse effects of CGRP imposed on NP cells, which were confirmed in vitro and in vivo. Our results will bring about a brand-new insight into the roles of neuromodulation in IVDD and related therapeutic attempts.

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Section: Introductionmentioning

confidence: 99%

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

Sun

Zhu

Chang

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…IVDD, a common but complex process, is frequently associated with LBP. Evidence showed that the pro-inflammatory microenvironment played a critical role in IVDD progression and LBP development ( Zhang et al, 2021a ; Lyu et al, 2021 ). Multiple anti-cytokine agents and signaling pathway inhibitors were investigated to ameliorate IVD inflammation and delay IVDD in preclinical and clinical studies ( Risbud et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

HSP90 Inhibitor 17-AAG Attenuates Nucleus Pulposus Inflammation and Catabolism Induced by M1-Polarized Macrophages

Zhang

Wang

et al. 2022

Front. Cell Dev. Biol.

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Overactivated inflammation and catabolism induced by proinflammatory macrophages are involved in the pathological processes of intervertebral disc (IVD) degeneration (IVDD). Our previous study suggested the protective role of inhibiting heat shock protein 90 (HSP90) in IVDD, while the underlying mechanisms need advanced research. The current study investigated the effects of HSP90 inhibitor 17-AAG on nucleus pulposus (NP) inflammation and catabolism induced by M1-polarized macrophages. Immunohistochemical staining of degenerated human IVD samples showed massive infiltration of macrophages, especially M1 phenotype, as well as elevated levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)13. The conditioned medium (CM) of inflamed NP cells (NPCs) enhanced M1 polarization of macrophages, while the CM of M1 macrophages but not M2 macrophages promoted the expression of inflammatory factors and matrix proteases in NPCs. Additionally, we found that 17-AAG could represent anti-inflammatory and anti-catabolic effects by modulating both macrophages and NPCs. On the one hand, 17-AAG attenuated the pro-inflammatory activity of M1 macrophages via inhibiting nuclear factor-κB (NF-κB) pathway and mitogen-activated protein kinase (MAPK) pathways. On the other hand, 17-AAG dampened M1-CM-induced inflammation and catabolism in NPCs by upregulating HSP70 and suppressing the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, both in vitro IVD culture models and murine disc puncture models supported that 17-AAG treatment decreased the levels of inflammatory factors and matrix proteases in IVD tissues. In conclusion, HSP90 inhibitor 17-AAG attenuates NP inflammation and catabolism induced by M1 macrophages, suggesting 17-AAG as a promising candidate for IVDD treatment.

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“…The main reasons associated with IVDD include nutritional, environmental, and genetic factors [ 11 , 12 ]. These factors lead to changes in cell morphology, inflammation, an increase in senescence cells, apoptosis, and autophagy [ 13 , 14 , 15 , 16 , 17 , 18 ]. IVDD is characterized by a loss of NP cells (more rounded chondrocyte-like cells) and their replacement by cells with a fibroblast-like phenotype [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Therapy for Intervertebral Disc Degeneration

Roh

Darai

Kyung

et al. 2021

IJMS

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Intervertebral disc (IVD) degeneration can cause chronic lower back pain (LBP), leading to disability. Despite significant advances in the treatment of discogenic LBP, the limitations of current treatments have sparked interest in biological approaches, including growth factor and stem cell injection, as new treatment options for patients with chronic LBP due to IVD degeneration (IVDD). Gene therapy represents exciting new possibilities for IVDD treatment, but treatment is still in its infancy. Literature searches were conducted using PubMed and Google Scholar to provide an overview of the principles and current state of gene therapy for IVDD. Gene transfer to degenerated disc cells in vitro and in animal models is reviewed. In addition, this review describes the use of gene silencing by RNA interference (RNAi) and gene editing by the clustered regularly interspaced short palindromic repeats (CRISPR) system, as well as the mammalian target of rapamycin (mTOR) signaling in vitro and in animal models. Significant technological advances in recent years have opened the door to a new generation of intradiscal gene therapy for the treatment of chronic discogenic LBP.

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The role of structure and function changes of sensory nervous system in intervertebral disc-related low back pain

Cited by 58 publications

References 129 publications

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

HSP90 Inhibitor 17-AAG Attenuates Nucleus Pulposus Inflammation and Catabolism Induced by M1-Polarized Macrophages

Genetic Therapy for Intervertebral Disc Degeneration

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