Pathomechanism of the IVDs Degeneration and the Role of Neurotrophic Factors and Concentration of Selected Elements in Genesis of Low Back Pain

Curr Pharm Biotechnol. 2023;24(9):1164-1177. doi: 10.2174/1389201024666221021142904.

Abstract

Degenerative disc disease of the lumbosacral spine is a very common medical problem. An episode of sciatica occurs at least once in the life of 60-90% of the human population. A phenomenon that is closely related to the process of lowering the pH of the extracellular matrix degenerating the intervertebral disc (IVD) is the precipitation of calcium salts, especially pyrophosphate dehydrate and hydroxyapatite. In such an altered environment of the IVD, we can observe an increased influx of monocytes, macrophages, T-lymphocytes, as well as non-immunocompetent cells, which are a source of cytokines, e.g., tumor necrosis alpha (TNF-α), interleukin- (IL-1β, IL-8). The above-mentioned mediators of an inflammatory condition contribute to an increase in the expression of Brain-Derived Neurotrophic Factor (BDNF) and Glial cell Derived Neurotrophic Factor (GDNF) in mast cells and chondrocytes, as well as to the descending transport of these mediators along the nerve endings. In the process of degeneration of the IVD as a result of repeated and even slight injuries, there is damage to the connections of the endplate of the vertebral bodies with the IVD, which results in an impairment of the penetration of nutritional substances and water into the disc. As a consequence, there is an overexpression of the brain-derived neurotrophic factor GDNF, as well as neuromodulin (GAP-43) in the mast cells and chondrocytes of the IVDs, while descending transport of these mediators along the nerve fibers is also observed.

Keywords: Interverbal discs; brain-derived neurotrophic factor; calcium; degeneration; glial cell derived neurotrophic factor; molecular marker; nerve endings.

MeSH terms

  • Brain-Derived Neurotrophic Factor / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Humans
  • Intervertebral Disc Degeneration*
  • Intervertebral Disc*
  • Low Back Pain* / metabolism
  • Low Back Pain* / pathology

Substances

  • Brain-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor