26/05/2023
Intervertebral Disc: Healthy v. Degenerated - Analysis by Physio Meets Science
“👉 Intervertebral Disc Degeneration (IVD) is a multi-factorial process that involves alterations in biomechanics, the structure of the extracellular matrix (ECM), and genetic and cellular activity. https://www.hindawi.com/journals/bmri/2016/5952165/, https://www.oarsijournal.com/article/S1063-4584(15)00877-8/fulltext
IVD degeneration is often asymptomatic https://pubmed.ncbi.nlm.nih.gov/25430861/, https://pubmed.ncbi.nlm.nih.gov/8208267/, whereas degenerative disc disease (DDD) is defined by some authors when IVD degeneration progresses to being symptomatic, for example, through pain resulting from nerve ingrowth into the IVD. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)02135-1/fulltext, https://www.sciencedirect.com/science/article/pii/S0021929022003013
👉 In the intact IVD, the nucleus pulposus matrix mostly contains proteoglycans (PG) and non-oriented collagen type II fibers. https://pubmed.ncbi.nlm.nih.gov/35846355/
👉 The proteoglycans contain negatively charged sulfated groups leading to an intradiscal osmotic pressure crucial for the basal hydration of the NP and the biomechanical function of the IVD. https://pubmed.ncbi.nlm.nih.gov/31556329/, https://pubmed.ncbi.nlm.nih.gov/11292372/
👉 Within the degenerated disc, the total content of PG decreases. Small non-aggregating PGs are present. This drop-in PG content reduces the water-binding capacity of the disc and leads to a reduction of the intervertebral disc pressure (IDP) https://www.sciencedirect.com/.../abs/pii/0304416581904761, https://link.springer.com/article/10.1007/s003300000556
👉 This reduced IDP an increase the deformation of the AF, leading to tears, delamination and fissures (https://journals.lww.com/spinejournal/Abstract/2006/08150/What_is_Intervertebral_Disc_Degeneration,_and_What.24.aspx). Additionally, the loss in water content can result in a reduction in the IVD height (approximately 3 % per year) (https://onlinelibrary.wiley.com/doi/10.1111/j.1469-7580.2012.01551.x), which can compromise the load-carrying ability of the IVD, and load transfer through the spinal column, leading to degeneration in structures such as the facet joints.
👉 Additionally, during disc degeneration, the production of catabolic cytokines,matrix-degrading enzymes, and neurotrophic as well as angiogenic factors occur due to cellular changes. https://pubmed.ncbi.nlm.nih.gov/25748081/, https://pubmed.ncbi.nlm.nih.gov/33445782/, https://pubmed.ncbi.nlm.nih.gov/18397957/
👉 This can lead to blood and nerve vessel ingrowth in the annulus fibrosus (AF). https://pubmed.ncbi.nlm.nih.gov/18727839/, https://pubmed.ncbi.nlm.nih.gov/20690185/, https://pubmed.ncbi.nlm.nih.gov/25209447/
👉 The AF is composed of highly oriented concentric lamella of type I collagen whereas the cell density is higher in intact than in degenerated discs. https://pubmed.ncbi.nlm.nih.gov/35846355/
👉 Native disc in intact IVD cells produce a plethora of cytokines and chemokines expressing the corresponding receptors and maintaining homeostasis in a para and autocrine manner. https://pubmed.ncbi.nlm.nih.gov/25748081/ The cartilaginous endplate (CEP) is intact with blood vessels. The NP has a high number of proteoglycans. AF cells aligned. https://pubmed.ncbi.nlm.nih.gov/15987475/
👉 Degenerated IVDs: shift to a catabolic environment. Cytokines are expressed by disc cells themselves. https://pubmed.ncbi.nlm.nih.gov/25748081/
The CEP has a higher amount of blood vessels than in the intact IVD. Proteoglycan number decreases in the NP. In the AF, there is a loss of alignment and support for AF cells. https://pubmed.ncbi.nlm.nih.gov/32210719/
👉 As soon as the AF or CEP is ruptured during injury or disc degeneration, a route for migration of immune cells into the IVD is provided. Immune cells, including T cells, B cells, macrophages, neutrophils and mast cells, contribute to an inflamed environment within the disc, further increasing the cytokine and chemokine expression and leading to a viscous circle of inflammatory driven catabolism. A crack in CEP allows blood vessels to grow into the AF and NP. https://pubmed.ncbi.nlm.nih.gov/29708266/
The AF herniates/bulges, which is where blood vessel ingrowth primarily occurs.”
Figures: https://www.sciencedirect.com/science/article/pii/S0021929022003013
