Literature ReviewCytokine Involvement in Biological Inflammation Related to Degenerative Disorders of the Intervertebral Disk: A Narrative Review
Introduction
Intervertebral disk (IVD) degeneration (IDD) is an irreversible and progressive process with disabling potential as a result of pain. It is implicated to play a clinical role in the presentation of low back pain (LBP) and lumbar radiculopathy secondary to IVD displacement.1 Age, mechanical pressures, genetics, inflammatory and biochemical changes can all act as triggering agents in this condition.1, 2, 3, 4
Degenerative disorder of the disk is characterized generally as enhanced matrix degradation, angiogenesis/neovascularization, nerve ingrowth, and increased expression of catabolic cytokines, resulting in anatomic and biochemical disk changes.1, 2, 5, 6, 7 The condition may include disk desiccation, decreased disk height, disk bulging, annular fissures, osteophytes, or end plate sclerosis.8 The disk’s nucleus pulposus (NP) is filled with proteoglycans as the surrounding annulus fibrosis (AF) is collagenous. The aged disk has less water, supposedly as a result of loss of negatively charged proteoglycans, consequently affecting one’s ability to bear loads.2, 9 The disk is largely avascular and aneural besides the outer third of the annulus. However, degeneration accompanies the growth of blood vessels and nerves into the inner layers of annulus and nucleus.5, 6, 7
It is now well established that in chronic inflammation the disk experiences extracellular matrix (ECM) loss and degradation. Because the inflammatory cascade involves neovascularization and nerve ingrowth, macrophages are seen as the most populous of any inflammatory cell.10, 11, 12, 13, 14 Once macrophages are activated, they secrete cytokines and disk-degenerative compounds and may even spread to nearby noninjured disk tissue.10, 13 Nonresolved neuroinflammation may play a key role in the development of chronic progressive pain.15 The purpose of this narrative literature review is to discuss the literature regarding the potential role that cytokines play in degenerative disk disease.
Section snippets
Methods
This was a narrative overview. A search was performed using electronic databases: PubMed, Google Scholar, and EBSCOhost generated articles relevant to cytokines and their role in degeneration. Studies were limited to those published in the last 3 decades that had free full-text available online in English. The final selection of studies ranged from 1994 through March 13, 2017. Search terms included “intervertebral disc degeneration,” “cytokines,” and “inflammatory mediators.” EBSCOhost
IVD Degeneration
Healthy ECM undergoes a normal cycle of tissue degradation and synthesis. Nutritional compromise, repetitive loading, or natural aging may lead to a disk wearing down as normal matrix turnover loses its remodeling capability, and structural proteins degrade in excess.1 In turn, the disk loses hydration and its structural integrity. Disk degeneration likely involves biochemical and mechanical cell stimulation that activates this matrix destructive pathway.2 Fig 1 provides a representation of the
Discussion
There is a complex interworking among proinflammatory mediators, collectively participating in the pathologic expressions behind LBP. Inflammation, blood and nerve ingrowth, tissue breakdown, and pain processing all have cytokine involvement. The secretion of cytokines and disk degenerative enzymes may result in disk resorption, degeneration, and neuropathic pain.
A nerve may need to be inflamed to experience pain, because nerve compression alone may simply result in sensory and motor deficits.
Conclusion
Cytokines may have an important role in the biochemical mechanisms related to IDD.
Funding Sources and Conflicts of Interest
No funding sources or conflicts of interest were reported for this study.
Contributorship Information
Concept development (provided idea for the research): C.M.D.
Design (planned the methods to generate the results): C.M.D.
Supervision (provided oversight, responsible for organization and implementation, writing of the manuscript): C.M.D.
Data collection/processing (responsible for experiments, patient management, organization, or reporting data): C.M.D.
Analysis/interpretation (responsible for statistical analysis, evaluation, and presentation of the results): C.M.D.
Literature search (performed
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