Disc inflammation potentially promotes axonal regeneration of dorsal root ganglion neurons innervating lumbar intervertebral disc in rats

Spine (Phila Pa 1976). 2004 Dec 1;29(23):2621-6. doi: 10.1097/01.brs.0000146051.11574.b4.

Abstract

Study design: The expression of growth-associated protein 43 (GAP-43), a marker of axonal growth, in the dorsal root ganglion (DRG) neurons innervating the lumbar intervertebral disc was assessed using the retrograde tracing method and immunohistochemistry.

Objectives: To study whether disc inflammation affects GAP-43 expression in DRG neurons innervating the disc in rats.

Summary and background data: Persistent inflammation and nerve ingrowth into the inner layer of degenerated discs can be a cause of discogenic pain. Although the presence of GAP-43-expressing nerve fibers in painful discs has been reported, the expression of GAP-43 in DRG neurons innervating the disc has not been studied.

Methods: Seven days after the application of Fluoro-Gold to the L5-L6 disc, 50 microL of saline (n = 10, control group) or complete Freund's adjuvant (n = 10, inflammatory group) was applied to the disc in rats. Ten days after the Fluoro-Gold application, T13-L5 DRGs were double-stained with GAP-43 and either calcitonin gene-related peptide or isolectin B4 (IB4).

Results: The percentage of Fluoro-Gold-labeled neurons that were positive for GAP-43 was significantly higher in the inflammatory group (44%) than in the control group (24%, P < 0.001). In both groups, the majority of GAP-43-positive neurons were small and positive for calcitonin gene-related peptide but not IB4.

Conclusions: The present results suggest that disc inflammation potentially promotes axonal growth of DRG neurons innervating the disc. In light of the strong correlation between the expression of calcitonin gene-related peptide and nerve growth factor receptor, it is most likely that nerve growth factor-sensitive DRG neurons extend their axons following disc inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / pathology
  • Biomarkers / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Discitis / chemically induced
  • Discitis / metabolism*
  • Discitis / pathology
  • Disease Models, Animal
  • Freund's Adjuvant / pharmacology
  • GAP-43 Protein / metabolism
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / innervation*
  • Lumbar Vertebrae*
  • Male
  • Neurons / metabolism*
  • Neurons / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration
  • Stilbamidines / metabolism

Substances

  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Biomarkers
  • GAP-43 Protein
  • Stilbamidines
  • Freund's Adjuvant
  • Calcitonin Gene-Related Peptide