The pathophysiology of disc degeneration

Abstract

The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries. This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

“…Intervertebral disc degeneration (IDD) is characterized by damage of the disc structure, progressive loss of water content and proteoglycan in the extracellular matrix (ECM) (1). IDD is considered a predominant source of spine-related diseases and chronic lower back pain, which causes a major economic and social burden affecting millions of people worldwide (2).…”

“…The peripheral annulus fibrosis encases the nucleus pulposus and is rich in type I collagen. The cartilaginous endplates contain the peripheral vasculature, which can nourish the disc (1). The main morphological manifestations of IDD are vertebral instability, disc herniation and spinal stenosis (8).…”

“…Several factors, such as biological, mechanical and genetic factors, are widely considered as significant contributors to the disc degenerative process (1). For example, Bachmeier et al (13) identified that matrix metalloproteinase-3 (MMP-3), which was essential for matrix degeneration, had an essential role in lumbar disc herniation and degeneration.…”

Ex vivo observation of human intervertebral disc tissue and cells isolated from degenerated intervertebral discs

“…Indeed, the degenerative process of the disc begins as early as the second decade of life, with most of the lumbar discs showing some evidence of degeneration by the fifth decade [1,2].…”

Effects of methylene blue on postoperative low-back pain and functional outcomes after lumbar open discectomy: a triple-blind, randomized placebo-controlled trial

“…53 Different theories underlie the pharmacological and therapeutic mechanisms that may be responsible for the effect of MB, including the inhibition of free-radical generation, 16 deactivation of xanthine oxidase, 41 inhibition of the production of nitric oxide (which has been implicated in the inflammatory processes of disc degeneration and discogenic pain), 4,17,25 destruction of free nociceptive nerve endings for the relief of pain, 27,50 reduction of neurotoxic structural and functional damage in brain parenchyma, 38 its effectiveness as a neuroprotective compound, 51 its anxiolytic and antidepressant activities, 18,28,42 and inhibition of monoamine oxidase (MAO). 52 The mechanism by which MB exerts its anxiolytic and antidepressant effects has been linked to actions on MAO-A as well as nitric oxide synthase.…”