What is Intervertebral Disc Degeneration (IVDD)?

Intervertebral disc degeneration (IVDD) refers to the gradual deterioration of the intervertebral discs, which are the soft, cushion-like structures located between the vertebrae of the spine. These discs act as shock absorbers, providing support and flexibility to the spine while allowing for movement and preventing the vertebrae from rubbing against each other.


Intervertebral disc degeneration is a common age-related condition that can also be influenced by genetic factors, lifestyle choices, and mechanical stress on the spine. Over time, the intervertebral discs may lose their water content, elasticity, and structural integrity, leading to various changes, including:


  • Loss of Disc Height: The degeneration of the intervertebral discs can result in a loss of disc height, causing the vertebrae to become closer together. This can lead to a reduction in the space available for the nerves exiting the spinal cord, potentially causing nerve compression and associated symptoms such as pain, numbness, or weakness in the arms or legs.


  • Changes in Disc Composition: With degeneration, the composition of the intervertebral discs may change, including a decrease in proteoglycan content (which helps retain water) and an increase in collagen content (which affects disc stiffness). These changes can contribute to decreased disc resilience and increased susceptibility to injury.


  • Formation of Disc Herniation: In some cases of severe degeneration, the outer layer of the intervertebral disc (annulus fibrosus) may weaken or tear, allowing the inner gel-like material (nucleus pulposus) to bulge or herniate outwards. Disc herniation can compress nearby spinal nerves, leading to symptoms such as back pain, sciatica, or radiculopathy.


  • Osteophyte Formation: As a response to degeneration and instability in the spine, the body may form bony outgrowths called osteophytes, also known as bone spurs. Osteophytes can develop along the edges of the vertebral bodies and the intervertebral discs, potentially causing further compression of spinal nerves and contributing to pain and stiffness.


  • Reduced Disc Function: As the intervertebral discs degenerate, they may become less effective at absorbing shock and distributing forces within the spine during movement. This can lead to increased stress on the surrounding structures, including the facet joints, ligaments, and muscles, potentially resulting in pain, stiffness, and reduced mobility.


What is the relationship between IVDD and oxidative stress?

The relationship between intervertebral disc degeneration (IVDD) and oxidative stress is an emerging area of research that suggests oxidative stress plays a significant role in the pathogenesis and progression of IVDD. Here’s how oxidative stress is related to IVDD:


  • Cellular Damage and Degeneration: Oxidative stress can lead to cellular damage within the intervertebral discs by causing oxidative modifications to important cellular components such as lipids, proteins, and DNA. These oxidative modifications can impair cellular function, disrupt cellular signaling pathways, and contribute to the breakdown of extracellular matrix proteins within the disc. Over time, this cellular damage can accelerate the degenerative process in the intervertebral discs, leading to structural changes and loss of disc integrity.


  • Loss of Proteoglycans and Water Content: Oxidative stress has been shown to decrease the synthesis of proteoglycans, which are essential components of the extracellular matrix within intervertebral discs. Proteoglycans help to maintain the hydration and osmotic pressure within the disc, which is crucial for its ability to absorb shock and resist compression. Reduced proteoglycan synthesis due to oxidative stress can lead to a decrease in water content within the disc, resulting in decreased disc height and impaired mechanical properties.


  • Activation of Inflammatory Pathways: Oxidative stress can trigger inflammatory responses within the intervertebral discs, leading to the production of pro-inflammatory cytokines, chemokines, and matrix metalloproteinases (MMPs). These inflammatory mediators can further exacerbate oxidative stress and promote tissue degradation within the disc by activating catabolic pathways and degrading extracellular matrix proteins. Chronic inflammation and oxidative stress within the disc microenvironment can contribute to the progression of IVDD and associated symptoms such as pain and stiffness.


  • Senescence and Cellular Aging: Oxidative stress has been implicated in the cellular senescence and premature aging of disc cells (including nucleus pulposus cells and annulus fibrosus cells). Cellular senescence is associated with a decline in cellular function, reduced capacity for tissue repair, and increased susceptibility to degenerative changes. Oxidative stress-induced cellular senescence may contribute to the loss of regenerative capacity within the intervertebral discs and accelerate the degenerative process in IVDD.


Overall, oxidative stress appears to play a key role in the pathogenesis and progression of intervertebral disc degeneration by promoting cellular damage, inflammation, loss of proteoglycans, and cellular senescence within the disc microenvironment.