Propionibacterium acnes contributes to low back pain via upregulation of NGF in TLR2-NF-κB/JNK or ROS pathway

Jiao, Yucheng; Yan, Lin; Zheng, Jiancheng; Shi, Liqiang; Zheng, Yuehuan; Zhang, Ying; Li, Jitian; Chen, Zhe; Cao, Peng

doi:10.1016/j.micinf.2022.104980

Cited by 7 publications

(9 citation statements)

References 38 publications

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“…As an important neuropeptide, NGF is strongly correlated with discogenic LBP. In our previous study, we found that Propionibacterium acnes -infected IVD produced large quantities of NGF and the increased NGF was the primary factor involved in LBP [ 10 ]. Recently, specific antibodies directed against NGF were used for therapy of LBP [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…In accordance with our previous study [ 10 ], rat L1 to L3 DRGs were harvested to analyze the gene expression of substance P (SP) and calcitonin gene-related peptide (CGRP), because bilateral L1–L3 DRGs innervate the lower IVDs [ 14 ]. In brief, the TRIzol reagent (Invitrogen, Life Technologies Corporation, CA, USA) was used to extract the total RNA, and the cDNA was produced with reverse transcriptase kit (TaKaRa, Shiga, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…One of the potential mechanisms for LBP involves upregulation of pain-related peptide, for example, nerve growth factor (NGF) [ 10 , 11 ]. For example, NGF participated in bacteria-induced or degeneration-related LBP [ 10 , 11 ]. Thus, we hypothesized that wogonin may attenuate LBP via regulating the NGF expression.…”

Section: Introductionmentioning

confidence: 99%

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Wogonin, a Bioactive Ingredient from Huangqi Guizhi Formula, Alleviates Discogenic Low Back Pain via Suppressing the Overexpressed NGF in Intervertebral Discs

Duan

Chai

et al. 2023

Mediators of Inflammation

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Purpose. To investigate whether wogonin, a key bioactive ingredient of Huangqi Guizhi formula (HQGZ formula; a Traditional Chinese Medicine herbal formula) according to network pharmacology analysis, has analgesic effects on discogenic low back pain (LBP) via regulating the nerve growth factor (NGF) in intervertebral discs (IVDs). Methods. The lumbar IVDs of rats were punctured to discogenic LBP, and the therapeutic effect of orally administrated HQGZ for discogenic LBP was investigated by measuring mechanical and cold allodynia and histological analysis. A network pharmacology analysis was conducted to search for bioactive ingredients from the HQGZ formula, and wogonin was suggested to be the most possible bioactive ingredient for LBP treatment. Subsequently, the analgesic effect of wogonin was investigated in the LBP model, and the gene expression of propain peptides in the bilateral dorsal root ganglia was analyzed using RT-PCR. Finally, immunohistochemical staining was performed for NGF expression of NGF in the IVDs to determine whether wogonin treatment would ameliorate NGF-induced LBP. Results. Oral administration of HQGZ for two weeks significantly ameliorated puncture-induced IVD degeneration (IDD) and LBP. In addition, the network pharmacology analysis revealed that wogonin, quercetin, and kaempferol were the potential candidate components of HQGZ for LBP treatment. Furthermore, we proved that wogonin had significant analgesic effects in the LBP model. Finally, wogonin was demonstrated to suppress the upregulated NGF in the IVD and ameliorate NGF-induced LBP in rats. Conclusions. The HQGZ formula has significant analgesic effects for LBP. In addition, the bioactive ingredient of wogonin was extracted from HQGZ and ameliorated LBP by suppressing the overexpressed NGF in degenerated IVDs. Therefore, wogonin has potential to be alternative treatment for LBP in clinical.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Wogonin, a Bioactive Ingredient from Huangqi Guizhi Formula, Alleviates Discogenic Low Back Pain via Suppressing the Overexpressed NGF in Intervertebral Discs

Duan

Chai

et al. 2023

Mediators of Inflammation

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“…Recent evidence with rat models with P. acnes inoculation showed the overexpression of SP, CGRP, IL-1β, IL-6, and IL-8 via the TLR2/NF-kb p65 pathway from NP cells induced discogenic back pain [127,128]. P. acnes was also associated with the upregulation of NGF expression via the TLR2-NF-kB/JNK pathway, which may contribute to the discogenic pain observed in rat models [129].…”

Section: Emerging Pathophysiologymentioning

confidence: 97%

Updates on Pathophysiology of Discogenic Back Pain

Jha,

Bernstock,

Chalif

et al. 2023

JCM

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Discogenic back pain, a subset of chronic back pain, is caused by intervertebral disc (IVD) degeneration, and imparts a notable socioeconomic health burden on the population. However, degeneration by itself does not necessarily imply discogenic pain. In this review, we highlight the existing literature on the pathophysiology of discogenic back pain, focusing on the biomechanical and biochemical steps that lead to pain in the setting of IVD degeneration. Though the pathophysiology is incompletely characterized, the current evidence favors a framework where degeneration leads to IVD inflammation, and subsequent immune milieu recruitment. Chronic inflammation serves as a basis of penetrating neovascularization and neoinnervation into the IVD. Hence, nociceptive sensitization emerges, which manifests as discogenic back pain. Recent studies also highlight the complimentary roles of low virulence infections and central nervous system (CNS) metabolic state alteration. Targeted therapies that seek to disrupt inflammation, angiogenesis, and neurogenic pathways are being investigated. Regenerative therapy in the form of gene therapy and cell-based therapy are also being explored.

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“…Jiao et al ( Jiao et al, 2019 ) reported that Propionibacterium acnes upregulated IL-8 secretion in NP cells by stimulating the TLR-2/NF-κB p56 pathway. In their subsequent study, these authors revealed the association of TLR2 and NF-κB p65/JNK pathways with nerve growth factor (NGF), a key pro-algesic factor ( Jiao et al, 2022 ).…”

Section: Relationships Between Inflammation and Iddmentioning

confidence: 99%

Natural products can modulate inflammation in intervertebral disc degeneration

Liu

Zhu²,

Liu³

et al. 2023

Front. Pharmacol.

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Intervertebral discs (IVDs) play a crucial role in maintaining normal vertebral anatomy as well as mobile function. Intervertebral disc degeneration (IDD) is a common clinical symptom and is an important cause of low back pain (LBP). IDD is initially considered to be associated with aging and abnormal mechanical loads. However, over recent years, researchers have discovered that IDD is caused by a variety of mechanisms, including persistent inflammation, functional cell loss, accelerated extracellular matrix decomposition, the imbalance of functional components, and genetic metabolic disorders. Of these, inflammation is thought to interact with other mechanisms and is closely associated with the production of pain. Considering the key role of inflammation in IDD, the modulation of inflammation provides us with new options for mitigating the progression of degeneration and may even cause reversal. Many natural substances possess anti-inflammatory functions. Due to the wide availability of such substances, it is important that we screen and identify natural agents that are capable of regulating IVD inflammation. In fact, many studies have demonstrated the potential clinical application of natural substances for the regulation of inflammation in IDD; some of these have been proven to have excellent biosafety. In this review, we summarize the mechanisms and interactions that are responsible for inflammation in IDD and review the application of natural products for the modulation of degenerative disc inflammation.

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Propionibacterium acnes contributes to low back pain via upregulation of NGF in TLR2-NF-κB/JNK or ROS pathway

Cited by 7 publications

References 38 publications

Wogonin, a Bioactive Ingredient from Huangqi Guizhi Formula, Alleviates Discogenic Low Back Pain via Suppressing the Overexpressed NGF in Intervertebral Discs

Wogonin, a Bioactive Ingredient from Huangqi Guizhi Formula, Alleviates Discogenic Low Back Pain via Suppressing the Overexpressed NGF in Intervertebral Discs

Updates on Pathophysiology of Discogenic Back Pain

Natural products can modulate inflammation in intervertebral disc degeneration

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