- *Corresponding Author:
- Wei Qi
Department of Acupuncture-Moxibustion and Tuina, Changchun University of Chinese Medicine, Jilin, Changchun 130117, China
E-mail: ljyzz3309@163.com
This article was originally published in a special issue, “Emerging Therapeutic Interventions of Biopharmaceutical Sciences” |
Indian J Pharm Sci 2024:86(3) Spl Issue “310-318” |
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms
Abstract
Increasing progress has been made in the research and treatment of cervical spondylosis. Traditional Chinese medicine has been shown to be effective as a complementary alternative therapy for the treatment of cervical spondylosis. However, the intervention mechanism of traditional Chinese medicine in the treatment of cervical spondylosis is still unclear. The aim of this review is to sort out the current knowledge on the mechanisms of traditional Chinese medicine for the treatment of cervical spondylosis, including acupuncture, needle-knife, manipulation, herbal treatments, and commonly used animal models of cervical spondylosis. Finally, the review will discuss the dilemmas faced by traditional Chinese medicine in the treatment of cervical spondylosis, as well as the shortcomings and future directions of traditional Chinese medicine in the treatment of cervical spondylosis.
Keywords
Cervical spondylosis, Chinese medicine, non-steroidal anti-inflammatory drugs, apoptosis, protein kinase B
Cervical spondylosis is a common degenerative spinal condition that can cause postural adjustment difficulties and balance perception deficits[1]. According to modern medical research, cervical spondylosis is closely linked to Intervertebral Disc Degeneration (IDD)[2]. IDD is a common age-related phenomenon that typically begins after the age of 45 and progresses continuously. The incidence of cervical spondylosis is gradually increasing due to changes in modern lifestyles and work patterns, affecting more and more young people[3]. For instance, cervical spondylosis affects a significant proportion of high school students, with an incidence rate of up to 48.9 %. This condition can cause symptoms such as pain in the neck, shoulders, and occipital region, as well as activity restrictions, which can significantly reduce the patient's quality of life[4,5]. Early intervention and treatment of cervical spondylosis is crucial in slowing down the course of the disease and improving the quality of life of patients.
Currently, pain and other related symptoms caused by cervical spondylosis are often managed by systemic and topical application of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)[6]. However, long-term use of such drugs may lead to side effects such as dyspepsia, gastritis, gastroduodenal ulcers, and bleeding; therefore, there is an urgent need to develop a more convenient and effective treatment strategy with fewer side effects. Traditional Chinese Medicine (TCM) therapies such as acupuncture, herbal medicine and tuina have been used clinically for >1000 y and are considered effective alternatives for the treatment of a wide range of diseases. The mechanisms of TCM in the treatment of cervical spondylosis are diverse, and although the specific mechanisms of action of different TCM therapies still need to be further clarified, TCM has shown positive results in the treatment of cervical spondylosis in recent years. The aim of this article is to review the mechanism of action of TCM in the treatment of cervical spondylosis, with a view to providing new insights into the treatment and research of this disease.
Animal Research
Currently, our understanding of the pathogenesis of cervical whiplash is limited. Treatment guidelines are currently limited to symptomatic relief due to legal, ethical, and moral constraints that make it difficult to use human tissue for scientific research. Animal models are ethically used in basic research and play an important role in bridging basic experiments with the clinic. Two key animal models for studying cervical disc degeneration are the rat surgical model and the rabbit non-invasive model. Each model has unique advantages and applicable scenarios. The rat surgical model directly simulates cervical degeneration through surgical means, which is highly simulative and controllable. It is particularly suitable for in-depth investigation of the pathological mechanisms of cervical degeneration and evaluation of therapeutic approaches. This model enables precise control over the location and extent of intervention, facilitating detailed pathological and biomechanical assessments. In contrast, the rabbit non-invasive model induces cervical degeneration physically and has the advantage of being simple and non-invasive, making it suitable for large-scale implementation and replication. This model enables the simulation of various stages of cervical degeneration and is appropriate for studying early pathological changes and evaluating non-invasive therapeutic approaches. In summary, the rat surgical model is suitable for in-depth studies of pathological mechanisms and treatment methods, while the rabbit non-invasive model is more appropriate for early studies of cervical spine degeneration and treatment evaluation. The appropriate selection and application of these two models is essential for a comprehensive understanding of the pathological process and treatment strategies for cervical disc degeneration. Table 1[7-22] summarizes the animal studies on the treatment of cervical spondylosis by TCM.
Animal model | Animals | Methodologies | Intervene | Machine | Bibliographic reference |
---|---|---|---|---|---|
Non-invasive model for low head position | New Zealand rabbit | The rabbits were positioned in a rabbit fixation box with their necks in a low head flexion position of 45°. Pathological changes in the neck structure were induced after cyclic modeling | Electro-acupuncture combined with gua sha method | Inhibition of the NF-κB/IkB/IKKβ pathway suppresses the expression of inflammatory factors, including IL-1β, IL-6, and TNF-α | [7] |
Non-invasive model for low head position | New Zealand rabbit | The rabbits were positioned in a rabbit fixation box with their necks in a low head flexion position of 45°. Pathological changes in the neck structure were induced after cyclic modeling | Needles | The expression of Wnt3α and β-catenin genes and proteins activates the Wnt/β-catenin signaling pathway and increases My-HC1 synthesis | [8] |
Non-invasive model for low head position | New Zealand rabbit | The rabbits were positioned in a rabbit fixation box with their necks in a low head flexion position of 45°. Pathological changes in the neck structure were induced after cyclic modeling | Herbal | Inhibition of NF-κB signaling pathway to release inflammatory factors such as IL-1, IL-6 and TNF-α | [9] |
Invasive neck surgery model | SD rats | A surgical model of the neck was created in rats and anaesthetized to remove specific muscles and ligaments, resulting in pathological changes in the neck structures | Massage | Attenuating the inflammatory response and apoptosis of intervertebral disc cells in rats with cervical spondylosis | [10] |
Non-invasive model for low head position | New Zealand rabbit | The rabbits were positioned in a rabbit fixation box with their necks in a low head flexion position of 45°. Pathological changes in the neck structure were induced after cyclic modeling | Needles | Downregulation of Notch1/DLL1 expression levels in muscle | [11] |
Invasive neck surgery model | SD rats | A surgical model of the neck was created in rats and anaesthetized to remove specific muscles and ligaments, resulting in pathological changes in the neck structures | Electro-acupuncture | Suppression of TNF-α and IL-6 expression in intervertebral disc chondrocytes by inhibiting the MCP-1/CCR2 signaling pathway | [12] |
Non-invasive model for low head position | New Zealand rabbit | The rabbits were positioned in a rabbit fixation box with their necks in a low head flexion position of 45°. Pathological changes in the neck structure were induced after cyclic modeling | Needles | Reduction of autophagy factor Beclin-1, PTEN gene and protein expression levels in cervical muscle of rabbits with cervical spondylosis | [13] |
Invasive neck surgery model | SD rats | A surgical model of the neck was created in rats and anaesthetized to remove specific muscles and ligaments, resulting in pathological changes in the neck structures | Herbal | Regulation of MKK3/6-p38MAPK signaling pathway and down-regulation of IL-6 and IL-8 content in chondrocytes within intervertebral discs | [14] |
Non-invasive model for low head position | New Zealand rabbit | The rabbits were positioned in a rabbit fixation box with their necks in a low head flexion position of 45°. Pathological changes in the neck structure were induced after cyclic modeling | Herbal | Inflammatory factors such as TNF-α, IL-1, IL-6 and other inflammatory factors released from the NF-κB signaling pathway are inhibited by altering the expression of miR-146a in the tissues of the posterior cervical muscle of model rabbits | [15] |
Invasive neck surgery model | New Zealand rabbit | The rabbits were positioned in a rabbit fixation box with their necks in a low head flexion position of 45°. Pathological changes in the neck structure were induced after cyclic modeling | Needles | Regulation of autophagy, apoptosis homeostasis in posterior cervical extensor muscle cells via PI3K/Akt signaling pathway | [16] |
Non-invasive model for low head position | New Zealand rabbit | The rabbits were positioned in a rabbit fixation box with their necks in a low head flexion position of 45°. Pathological changes in the neck structure were induced after cyclic modeling | Needles | Regulation of cartilage endplate integrin β1, p-FAK mRNA and protein expression, slowing down disc degeneration and re-establishing the mechanical balance of the cervical spine | [17] |
Invasive neck surgery model | SD rats | A surgical model of the neck was created in rats and anaesthetized to remove specific muscles and ligaments, resulting in pathological changes in the neck structures | Herbal | Activation of PPAR-γ pathway, inhibition of NF-κB signaling pathway, reduction of downstream inflammatory factor release | [18] |
Invasive neck surgery model | SD rats | A surgical model of the neck was created in rats and anaesthetized to remove specific muscles and ligaments, resulting in pathological changes in the neck structures | Electro-acupuncture | Inhibition of apoptotic cells in the intervertebral disc and increase in the expression level of Axin and β-catenin proteins | [19] |
Invasive neck surgery model | SD rats | A surgical model of the neck was created in rats and anaesthetized to remove specific muscles and ligaments, resulting in pathological changes in the neck structures | Electro-acupuncture | Up-regulation of Wnt1 and GSK-3 proteins inhibits apoptosis of intervertebral disc fibrous annulus cells in rats with cervical spondylosis model | [20] |
Invasive neck surgery model | SD rats | A surgical model of the neck was created in rats and anaesthetized to remove specific muscles and ligaments, resulting in pathological changes in the neck structures | Electro-acupuncture | Activation of PI3K/Akt pathway and inhibition of chondrocyte apoptosis in intervertebral discs | [21] |
Invasive neck surgery model | SD rats | A surgical model of the neck was created in rats and anaesthetized to remove specific muscles and ligaments, resulting in pathological changes in the neck structures | Herbal | Inhibition of inflammatory response and ECM degeneration through the MAPK pathway in a rat model of degenerative cervical intervertebral discs | [22] |
Table 1: Therapeutic mechanism of chinese medicine.
Due to the complex pathogenesis of cervical spondylosis and subjective symptoms such as restricted movement, current animal models are insufficient to fully describe the complete mechanism of this condition. In the future, it is important to consider not only the simulation and controllability of the model but also the complexity of the mechanism itself. This will allow us to fully incorporate the advantages of existing models and reduce their disadvantages. By doing so, we can establish a more comprehensive model that accurately simulates the multiple pathogenic mechanisms of cervical spondylosis. This will help us explore the therapeutic mechanism of Chinese medicine in a more in-depth manner.
Mechanisms of Chinese Medicine in the Treatment of Cervical Spondylosis
IDD is a complex process involving multiple factors such as changes in Extracellular Matrix (ECM) content, cellular aging and apoptosis, and cytokines. During this process, we observe a series of pathological changes such as increased degradation of the ECM and decreased synthesis of the matrix, decreased number of active cells, destruction of the disc's tissue structure, and functional damage[23]. In response to these key aspects, Chinese medicine has made significant progress in the treatment of cervical spondylosis in recent years, which can effectively relieve symptoms and restore the physiological function of neck structures. In view of the available research evidence, this article reviews the mechanisms of TCM in the treatment of cervical spondylosis as follows:
Regulation of inflammatory factor secretion:
The pathological progression of cervical spondylosis can be driven by a cycle of tissue damage and repair triggered by chronic inflammation, which in turn leads to tissue structural and functional dysfunction. In the process, a vicious cycle between degenerative disc changes and neck muscle imbalances accelerates disease progression. Abnormal activity of key inflammatory factors such as Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-1Beta (IL-1β), Prostaglandin E2 (PGE2), and IL-6, etc., within the intervertebral discs and muscles, not only exacerbates the local inflammatory response, but also leads to the development of the disease. That not only exacerbate the local inflammatory response but also drive the disease process[24]. Therefore, the treatment of cervical spondylosis needs to focus on the regulation of these inflammatory factors to achieve effective treatment by alleviating the vicious cycle of disc degeneration and muscle imbalance.
IL-6 is a cytokine that has various biological functions and plays a crucial role in inflammatory responses and immune regulation[25]. In the development of cervical spondylosis, IL-6 exacerbates the inflammatory state of the intervertebral discs and neck muscles through multiple mechanisms. Firstly, IL-6 promotes the activation and proliferation of inflammatory cells, leading to their accumulation in the damaged area. Subsequently, activated inflammatory cells release additional inflammatory mediators, which worsen the local inflammatory response. Furthermore, IL-6 affects the expression and synthesis of Matrix Metalloproteinases (MMPs), a group of enzymes that can degrade the ECM. Over-activation of MMPs leads to the destruction of the ECM, which exacerbates the structural damage to the discs and neck muscles. Destruction exacerbates the inflammatory response and impairs tissue function and repair[26]. Studies indicate that Wu Fu Drink, a TCM, may inhibit IL-6 expression and reduce MMP-3 expression, slowing down matrix degradation in intervertebral discs. According to[27], this action is expected to slow down the degeneration of intervertebral discs, thereby slowing down the process of IDD. Research has found that paralytic granules, a TCM item, can effectively alleviate inflammatory injury in the posterior cervical muscle of rats. The mechanism of action may be related to the activation of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) pathway and inhibition of the Nuclear Factor Kappa B (NF-κB) pathway, which in turn reduces the release of the inflammatory factor IL-6[18]. This finding provides a new therapeutic target for the treatment of damage to the power balance system in whiplash.
IL-1β, as a key member of the IL-1 family, plays an integral role in a variety of physiological and pathological responses in the body. Especially in skeletal muscle tissues, IL-1β is considered to be one of the most prominent inflammatory mediators[28]. By stimulating the release of other cytokines, it not only promotes and maintains the continuation of the inflammatory response, but also exacerbates muscle tissue damage in the context of chronic disease. In studies of degenerative disc disease, IL-1β stimulates the production of several pro-inflammatory mediators (e.g. cytokines, chemokines, and MMPs), as well as inducing cellular senescence and accelerating ECM degradation[29], a finding that positions it as a key mediator in the development of IDD. Further studies have shown a strong association between increased IL-1β and the onset of neck disease symptoms, emphasizing its central role in this disease mechanism. It has been shown that chiropractic manipulation reduces the inflammatory response of intervertebral disc cells and improves the progression of IDD in rats with cervical spondylosis[10], and its mechanism of action may be related to the inhibition of the IκB Kinase (IKK)/NF-κB pathway. Studies have shown that in a rabbit model of cervical spondylosis[15], different doses of Paeonia lactiflora and Glycyrrhiza glabra soup can effectively inhibit the NF-κB signaling pathway and reduce the expression of IL-1β inflammatory factors and microRNAs, which in turn alleviates the inflammatory neck injury caused by cervical spondylosis.
TNF-α is a crucial inflammatory factor in disc degeneration, with significantly higher levels in degenerated discs compared to normal discs[30]. It promotes degeneration by inducing the production and release of other inflammatory factors, increasing endothelial cell permeability, activating MMPs activity and gene expression, and inhibiting collagen and proteoglycan synthesis. Furthermore, TNF-α is strongly associated with muscle damage and pain levels. It can also impede the expression and activity of growth hormone and insulin-like growth factor, which hinders myoblast genesis and results in abnormal muscle damage[31]. The given effects demonstrate the significant role of TNF-α in IDD and muscle injury, indicating its potential as a therapeutic target. Chen et al.[32] applied tretinoin to a rat model of IDD and observed a reduction in the expression of TNF-α and MMP, which resulted in a slower degeneration of intervertebral discs in rats. According to[7], electroacupuncture combined with gua sha therapy may improve the pathological injury of neck muscles by down-regulating the expression of factors related to the NF-kB/IkB/IKKβ signaling pathway, which in turn reduces the expression of TNF-α inflammatory factors.
PGE2 plays a crucial role in the inflammatory process. It regulates pain sensation and inflammatory response, and also directly affects the inflammatory state of intervertebral discs and muscles[33]. PGE2 is released in inflammatory tissues during disc degeneration. It promotes the degeneration process and increases tissue sensitivity to pain-causing factors, contributing to the pain symptoms of cervical spondylosis[34]. The mechanism of action indicates that PGE2 has a dual function in regulating the inflammatory state of intervertebral discs and muscles, as well as in the formation of pain sensation in cervical spondylosis. Therefore, it is an important target for clinical diagnosis and treatment of this condition[35]. According to a study[36], needle knife intervention can significantly reduce the inflammatory expression of PGE2 in the muscle, which in turn improves neck muscle imbalance and slows down the process of disc degeneration. Additionally, the intervention can also reduce the expression level of PGE2 within the intervertebral disc, effectively alleviating symptoms associated with the neck. This result indicates that the needle knife intervention plays a significant role in regulating the inflammatory state of the neck and relieving the symptoms of cervical spondylosis.
In summary, it is evident that the administration of TCM and other treatments such as chiropractic and needle-knife interventions can slow down the progression of cervical spondylosis by modulating inflammatory factors and reducing disc degeneration and neck muscle damage. These findings suggest new strategies for the treatment of cervical spondylosis and highlight the significance of targeting inflammation modulation.
Inhibition of apoptosis:
Biomechanical factors, particularly long-term unbalanced flexion stress, play a crucial role in the degeneration of cervical intervertebral discs by inhibiting apoptosis. Stress can have negative effects on the intervertebral disc, including disturbances to stress distribution, internal pressure, and nutrient metabolism. Additionally, stress can cause injuries to the cervical muscle groups, such as spasm and ischemia, which can disrupt the dynamic balance of the neck. These injuries can aggravate the degeneration of the intervertebral discs and accelerate the development of cervical spondylosis[37].
It has been found by scholars that apoptosis of cervical muscle cells is a significant factor in the development of cervical spondylosis. The cervical muscles, intervertebral discs, and cervical segmental spinal cord neuronal cells are all subject to increased apoptosis, which is consistent with the degree of lesion strain[38]. Chondrocyte apoptosis in excess reduces the number of activated chondrocytes in the intervertebral disc. This affects their ability to synthesize or degrade ECM, leading to metabolite accumulation and insufficient nutrient supply. Consequently, IDD is triggered[39]. This passage describes how biomechanical and cell biological changes interact to exacerbate disc degeneration and promote the development of cervical spondylosis through apoptosis of cervical myocytes and intervertebral disc cells. Research has demonstrated that needle knife treatment can regulate the balance of apoptosis in posterior cervical extensor muscle cells through the Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (Akt) signaling pathway[16], which may be a potential target for needle knife repair of strained cervical muscles caused by cervical spondylosis. Research has demonstrated that needle knife intervention can effectively decrease the apoptosis rate of cervical nucleus pulposus cells in rabbits with cervical spondylosis[40], thereby aiding in the alleviation of IDD.
Therefore, it can be concluded that therapeutic means in TCM can effectively inhibit abnormal cell apoptosis in cervical muscles and intervertebral discs. This has a significant effect on repairing damaged cervical muscles and slowing down the pathological progression of cervical spondylosis.
Regulation of autophagy:
Autophagy is a mechanism present in all eukaryotic cells. Its central role is to synthesize essential parts by degrading intracellular components and recycling macromolecules during cell starvation[41]. Autophagy has gained much attention in the study of IDD, particularly under low-nutrient, low-pH, and low-oxygen conditions, where it is considered a key cell survival mechanism[42]. Although the role of autophagy in IDD is still debated, recent studies suggest that activating autophagy can have a protective effect[43]. This can reduce apoptosis, decrease ECM depletion, and inhibit inflammation and calcification of cartilage endplates[44]. In addition, autophagy and apoptosis occur simultaneously during skeletal muscle injury and repair, demonstrating the presence and importance of autophagy in various degenerative diseases and in the metabolic breakdown and remodeling of skeletal muscle. Autophagy also plays a role in the remodeling of skeletal muscle cells by participating in the process of cellular dedifferentiation, neo-division, and proliferation. This highlights the importance of autophagy in skeletal muscle repair[45].
A study conducted on a rabbit model of cervical spondylosis found that excessive activation of autophagy in cervical myocytes can cause damage to the organism[13]. However, the needle-knife treatment prevented autophagy-induced cell death by reducing the expression levels of autophagy-related proteins beclin-1 and PTEN. This promoted muscle repair and slowed down the pathological process of cervical spondylosis. Furthermore, the application of herbal hot compress treatment can improve the autophagy function of intervertebral disc cells and decrease cell apoptosis by upregulating the expression of beclin-1, Light Chain 3 (LC3), and B-Cell Lymphoma 2 (Bcl-2) and messenger Ribonucleic Acid (mRNA). This, in turn, mitigates disc degeneration and alleviates symptoms such as discomfort in the cervical spine. The study shows potential for further research into the prevention and treatment of cervical spondylosis[46].
Comprehensive analyses indicate that autophagy plays a crucial role in the development and therapeutic strategy of IDD. TCM therapeutic approaches effectively activate the autophagy pathway, promoting the repair of cervical muscles and demonstrating a significant role in preventing abnormal disc degeneration. However, the precise regulation of autophagy flux in cervical spondylosis remains an important focus for future research. In-depth exploration of the detailed changes in the autophagy process may aid in better understanding its mechanism of action in treating cervical spondylosis.
Improvement of cervical muscle fibrosis:
Long-term strain and degenerative changes in the neck can lead to the development of chronic inflammation. This, in turn, causes fibrosis of the neck muscles, which is the pathological basis for the mechanical imbalance in the neck[47]. After injury, fibroblasts and other stromal cells recruit myofibrils, the basic unit of skeletal muscle structure, to the site of injury and begin to deposit collagen (type I, etc.)[48]. Although skeletal muscle has a high regenerative capacity, excessive collagen deposition can lead to muscle fibrosis, which can impair skeletal muscle’s ability to regenerate. The process involves the conversion of fibrotic effector cells, including resident and circulating fibrotic progenitor cells, into myofibroblasts, which is promoted by Transforming Growth Factor-Beta (TGF-β) signaling. TGF-β signaling becomes particularly active 3 d-5 d after injury and may persist for days to weeks as multiple cell populations, including fibrotic effector cells, are recruited to the site of injury[49]. Therefore, inhibiting TGF-β signaling could delay the fibrotic response and promote the proliferation and recovery of functional myogenic fibers. This provides a potential strategy for treating mechanical homeostasis disorders in the neck.
Previous research has demonstrated that needle knife treatment can effectively down-regulate the expression of type I collagen in neck muscle tissues, thereby improving neck musculature fibrosis[50]. Modulating the Notch2/TGF-β1 signaling pathway can achieve this effect. Needle knife therapy not only directly affects the degree of fibrosis in the muscle tissue but also promotes the restoration of neck muscle health and function through specific molecular mechanisms, such as the regulation of the Notch2/TGF-β1 signaling pathway. This provides a scientific basis for the role of needle knife therapy in improving fibrosis in the neck muscle groups.
Comprehensive analyses suggest that prolonged neck strain may result in muscle fibrosis, which can affect the mechanical balance of the neck. TCM therapies, such as needle knife therapy, have been demonstrated to be effective in improving fibrosis in the neck muscle groups, thereby promoting muscle health and recovery. This presents a novel approach to treating neck mechanical balance disorders. However, further research and exploration are required to fully understand the mechanisms of action of TCM therapies and their potential applications.
Conclusion
In this paper, we have reviewed the potential mechanisms of Chinese medicine in the treatment of cervical spondylosis and provided an overview of current research progress. Considering the specific pathological characteristics of cervical spondylosis, and based on the hypothesis of an imbalance of dynamic and static forces in the neck, it is believed that the key mechanisms of TCM in treating cervical spondylosis may include improving autophagy and apoptosis, alleviating inflammation, and repairing cervical muscle fibrosis. With its unique therapeutic concepts, easy-to-use methods, low cost, and minimal side effects, TCM has shown great potential as an effective treatment for cervical spondylosis.
However, the use of TCM to treat cervical spondylosis faces challenges due to its complex mechanism of action, which involves multiple targets and pathways. The specific mechanism of TCM in treating cervical spondylosis is not yet fully understood. Therefore, there is an urgent need for an in-depth investigation into the mechanism of action of TCM in treating cervical spondylosis. This investigation should involve interdisciplinary collaboration, the use of large sample sizes, and multi-omics techniques. Such in-depth studies will help to improve the scientific basis of TCM in the treatment of cervical spondylosis and further promote its application and development in clinical practice.
Conflict of interests:
The authors declared no conflict of interests.
References
- Yang L, Yang C, Pang X, Li D, Yang H, Zhang X, et al. Mechanoreceptors in diseased cervical intervertebral disc and vertigo. Spine 2017;42(8):540-6.
[Crossref] [Google Scholar] [PubMed]
- Meziat-Filho N, Azevedo e Silva G, Coutinho ES, Mendonça R, Santos V. Association between home posture habits and neck pain in high school adolescents. J Back Musculoskelet Rehabil 2017;30(3):467-75.
[Crossref] [Google Scholar] [PubMed]
- GBD 2015 Disease and injury incidence and prevalence collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: A systematic analysis for the Global burden of disease Study 2015. Lancet 2016;388(10053):1545-602.
- Yang X, Karis DS, Vleggeert-Lankamp CL. Association between Modic changes, disc degeneration, and neck pain in the cervical spine: A systematic review of literature. Spine J 2020;20(5):754-64.
[Crossref] [Google Scholar] [PubMed]
- Zhuang L, Wang L, Xu D, Wang Z, Liang R. Association between excessive smartphone use and cervical disc degeneration in young patients suffering from chronic neck pain. J Orthop Sci 2021;26(1):110-5.
[Crossref] [Google Scholar] [PubMed]
- Bums RK, Shamsi Y, Nikhat S, Akhtar W. Hijamah (cupping therapy) for pain management in patients with cervical spondylosis. Altern Ther Health Med 2023;29(7):268-71.
[Google Scholar] [PubMed]
- Gao H, Zhao Z, Chen J. Effects of electroacupuncture combined with gua sha on cervical muscle inflammatory factors and NF-κB/IκB/IKKβ signaling pathway in rabbits with cervical spondylosis. J Huazhong Univ Sci Technol 2023;52(4):458-65.
- Zhang YW, Li JL, Li YZ. Effects of needle knife intervention on the expression of Wnt3α, β-catenin and MyHC1 in cervical multifidus muscle cells of rabbits with cervical spondylosis. Chin J Tradit Chin Med 2023;41(10):130-278.
- He J, Lin R, Zhang Y. Study on the effect and mechanism of Paeonia lactiflora and Glycyrrhiza glabra soup in alleviating inflammatory injury of rabbit cervical intervertebral disc by inhibiting NF-κB signaling pathway. Chin J Tradit Chin Med 2020;35(8):3885-9.
- Liang L, Wu C, Xia L. Investigation of the role of chiropractic therapy on inflammatory response and apoptosis of intervertebral disc cells in cervical spondylosis model rats based on IKKβ/NF-κB pathway. Chin J Tradit Med 2023,33(5):44-51.
- Li J, Li K, Zhang Y. Effects of acupuncture intervention on ultrasound imaging and Notch1/DLL1 expression in cervical muscles of rabbits with cervical spondylosis. Chin J Tradit Chin Med 2023;41(12):64-83.
- Peng J, Tan G, Lai L. Effects of electroacupuncture on intervertebral disc chondrocytes and MCP-1/CCR2 signaling pathway in rats with cervical spondylosis. World Tradit Chin Med 2019;14(6):1412-6.
- Liu F, Zhou F, Fang T. Effect of needle knife intervention on gene and protein expression of beclin-1 and PTEN in cervical muscle of rabbits with cervical spondylosis model. Chin J Tradit Chin Med 2019;34(9):4274-7.
- Cheng G, Jiang Y, Li B. Effects of Guiqi Xuebao capsules on chondrocytes in rats with cervical spondylosis model. World Tradit Chin Med 2020;15(16):2369-72.
- Chen J, Lin R, Zhang Y. Exploring the mechanism of action of Paeonia lactiflora and Glycyrrhiza glabra soup in the treatment of inflammatory injury of posterior cervical muscles in rabbits with cervical spondylosis based on the regulation of NF-κB signaling pathway by miR-146a. J Rehabil 202;30(3):206-11.
- Liu F, Fang T, Hong T. Effects of needle knife intervention on PI3K/Akt signalling pathway in cervical posterior extensor muscle cells of rabbits with cervical spondylosis. Chin J Tradit Chin Med 2020;35(2):918-22.
- Liu F, Yu J, Tang N. Effect of acupuncture intervention on the signaling pathway of cartilage endplate integrin β1-FAK mechanics in rabbits with cervical spondylosis. Chin J Tradit Chin Med 2020;38(1):20-259.
- Yang ST, Fan DH, Lin Y. Modulation of PPAR-γ/NF-κB pathway by Xiangpaitong granules to improve inflammatory injury of rat posterior cervical muscle. Global Chin Med 2023;16(5):831-7.
- Zheng C, Huang P, Liao J. Effects of electroacupuncture on β-catenin and Axin protein expression in intervertebral disc cells of rats with cervical spondylosis model. Shizhen Guomao Guomao 2015;26(5):1259-61.
- Huang P, Liao J, Zheng C. Effects of electroacupuncture on Wnt1 and GSK-3β proteins of intervertebral disc cells in rats with cervical spondylosis model. J Hunan Univ Tradit Chin Med 2015;35(5):59-62.
- Tong X, Zheng J, Liao J. Effects of electroacupuncture on intervertebral disc chondrocytes and PI3K/Akt signaling pathway in rats with cervical spondylosis. China J Basic Chin Med 2016;22(9):1232-5.
- Zhao K, Chen M, Liu T, Zhang P, Wang S, Liu X, et al. Rhizoma drynariae total flavonoids inhibit the inflammatory response and matrix degeneration via MAPK pathway in a rat degenerative cervical intervertebral disc model. Biomed Pharmacother 2021;138:111466.
[Crossref] [Google Scholar] [PubMed]
- Kirnaz S, Capadona C, Wong T. Fundamentals of intervertebral disc degeneration. World Neurosurg 2022;157:264-73.
[Crossref] [Google Scholar] [PubMed]
- Yin J, Huang Y, Gao G, Nong L, Xu N, Zhou D. Changes and significance of inflammatory cytokines in a rat model of cervical spondylosis. Exp Ther Med 2018;15(1):400-6.
[Crossref] [Google Scholar] [PubMed]
- Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nat Rev Rheumatol 2014;10(1):44-56.
[Crossref] [Google Scholar] [PubMed]
- Li Z, Yang H, Hai Y, Cheng Y. Regulatory effect of inflammatory mediators in intervertebral disc degeneration. Mediators Inflamm 2023;2023:6210885.
[Crossref] [Google Scholar] [PubMed]
- Shen X, Xia B, Wei J. Effect of Wu Fu drink on the expression of serum and disc inflammatory factors in rat models of intervertebral disc degeneration. China Tradit Chin Med Sci Technol 2020;27(4):525-8.
- Mern DS, Beierfuß A, Fontana J, Thome C, Hegewald AA. Imbalanced protein expression patterns of anabolic, catabolic, anti-catabolic and inflammatory cytokines in degenerative cervical disc cells: New indications for gene therapeutic treatments of cervical disc diseases. PLoS One 2014;9(5):e96870.
[Crossref] [Google Scholar] [PubMed]
- Xin J, Wang Y, Zheng Z, Wang S, Na S, Zhang S. Treatment of intervertebral disc degeneration. Orthop Surg 2022;14(7):1271-80.
- Wang Y, Che M, Xin J, Zheng Z, Li J, Zhang S. The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother 2020;131:110660.
[Crossref] [Google Scholar] [PubMed]
- Wang J, Leung KS, Chow SK, Cheung WH. Inflammation and age-associated skeletal muscle deterioration (sarcopaenia). J Orthop Transl 2017;10:94-101.
[Crossref] [Google Scholar] [PubMed]
- Chen J, Xuan J, Gu YT, Shi KS, Xie JJ, Chen JX, et al. Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo. Biomed Pharmacother 2017;91:208-19.
[Crossref] [Google Scholar] [PubMed]
- Gong Y, Qiu J, Jiang T, Li Z, Zhang W, Zheng X, et al. Maltol ameliorates intervertebral disc degeneration through inhibiting PI3K/AKT/NF-κB pathway and regulating NLRP3 inflammasome-mediated pyroptosis. Inflammopharmacology 2023;31(1):369-84.
[Crossref] [Google Scholar] [PubMed]
- Das UN. Bioactive lipids in intervertebral disc degeneration and its therapeutic implications. Biosci Rep 2019;39(10):BSR20192117.
[Crossref] [Google Scholar] [PubMed]
- Shang P, Tang Q, Hu Z, Huang S, Hu Y, Zhu J, et al. Procyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD-2 complex. J Cell Mol Med 2020;24(6):3701-11.
[Crossref] [Google Scholar] [PubMed]
- Wan CY, Song ZL, Yuan Z. Effects of needle knife intervention on serum levels of IL-8, TNF-α and PGE_2 in rabbits with cervical spondylosis model. Chin J Tradit Chin Med 2022;40(9):240-86.
- Cazzanelli P, Wuertz-Kozak K. MicroRNAs in intervertebral disc degeneration, apoptosis, inflammation, and mechanobiology. Int J Mol Sci 2020;21(10):3601.
[Crossref] [Google Scholar] [PubMed]
- Chen S, Lei L, Li Z, Chen F, Huang Y, Jiang G, et al. Grem1 accelerates nucleus pulposus cell apoptosis and intervertebral disc degeneration by inhibiting TGF-β-mediated Smad2/3 phosphorylation. Exp Mol Med 2022;54(4):518-30.
[Crossref] [Google Scholar] [PubMed]
- Shi S, Kang XJ, Zhou Z, He ZM, Zheng S, He SS. Excessive mechanical stress-induced intervertebral disc degeneration is related to Piezo1 overexpression triggering the imbalance of autophagy/apoptosis in human nucleus pulpous. Arthritis Res Ther 2022;24(1):119.
[Crossref] [Google Scholar] [PubMed]
- Chen B, Liu H, Zhang L. Visualized needle knife inhibits nucleus pulposus cell apoptosis and thus improves intervertebral disc degeneration in rabbits with cervical spondylosis. Acupuncture Res 2022;47(11):1005-11.
- Yurube T, Ito M, Kakiuchi Y, Kuroda R, Kakutani K. Autophagy and mTOR signaling during intervertebral disc aging and degeneration. JOR Spine 2020;3(1):e1082.
[Crossref] [Google Scholar] [PubMed]
- Kritschil R, Scott M, Sowa G, Vo N. Role of autophagy in intervertebral disc degeneration. J Cell Physiol 2022;237(2):1266-84.
[Crossref] [Google Scholar] [PubMed]
- Gong CY, Zhang HH. Autophagy as a potential therapeutic target in intervertebral disc degeneration. Life Sci 2021;273:119266.
[Crossref] [Google Scholar] [PubMed]
- Luo L, Jian X, Sun H, Qin J, Wang Y, Zhang J, et al. Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy. Stem Cells 2021;39(4):467-81.
[Crossref] [Google Scholar] [PubMed]
- Hao Y, Ren Z, Yu L, Zhu G, Zhang P, Zhu J, et al. p300 arrests intervertebral disc degeneration by regulating the FOXO3/Sirt1/Wnt/β-catenin axis. Aging Cell 2022;21(8):e13677.
[Crossref] [Google Scholar] [PubMed]
- Chen J, Gao H, Zhao Z. Expression of autophagy and apoptosis-related factors in rabbit intervertebral discs in a model of cervical spondylosis with hot compresses of traditional Chinese medicine. Chin Tissue Eng Res 2023;27(26):4181-6.
- Li Z, Liang Q, Li H, Lin X, Meng J, Yang D, et al. Fatty infiltration of the cervical multifidus musculature and its clinical correlation to cervical spondylosis. BMC Musculoskelet Disord 2023;24(1):613.
[Crossref] [Google Scholar] [PubMed]
- Mahdy MA. Skeletal muscle fibrosis: An overview. Cell Tissue Res 2019;375(3):575-88.
[Crossref] [Google Scholar] [PubMed]
- Chen W, You W, Valencak TG, Shan T. Bidirectional roles of skeletal muscle fibro-adipogenic progenitors in homeostasis and disease. Ageing Res Rev 2022;80:101682.
[Crossref] [Google Scholar] [PubMed]
- Liu H, Zhang Z, Zhang L. Exploring the effect of needle knife therapy on posterior cervical muscle fibrosis in rabbits with cervical spondylosis based on Notch2/TGF-β1 pathway. Fujian Tradit Chin Med 2023;54(3):14-8.