Disco intervertebrale

Comparison of the healthy and degenerated intervertebral disc (IVD).

IVD degeneration 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/.../S1063-4584(15.../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/.../PIIS0140-6736(97.../fulltext, https://www.sciencedirect.com/.../pii/S0021929022003013

In the intact IVD, the nucleus pulposus matrix mostly contains proteoglycans (PG) and non-oriented collagen type II ?bers. 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/.../What_is_Intervertebral_Disc...). Additionally, the loss in water content can result in a reduction in the IVD height (approximately 3 % per year) (https://onlinelibrary.wiley.com/.../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 ?brosus (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 in?amed environment within the disc, further increasing the cytokine and chemokine expression and leading to a viscous circle of in?ammatory 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/.../pii/S0021929022003013