Innervation of the lumbar intervertebral disc by nerve growth factor-dependent neurons related to inflammatory pain

Spine (Phila Pa 1976). 2004 May 15;29(10):1077-81. doi: 10.1097/00007632-200405150-00005.

Abstract

Study design: We used anatomic tracers and immunoreactivity in rats to define dorsal root ganglion neuron populations innervating the lumbar discs in physiologic and inflammatory states.

Objectives: To investigate the percentages of calcitonin gene-related peptide-immunoreactive (CGRP-ir) and isolectin B4 (IB4)-binding neurons innervating lumbar discs.

Summary of background data: Small neurons are classified into two types. One contains CGRP and expresses the nerve growth factor receptor. The other binds IB4 and expresses the glial cell line-derived neurotrophic factor receptor.

Methods: A neurotracer, Fluoro-Gold, was applied to the L5-L6 disc in rats. Five days later, 50-microL saline (control group: n = 8) or Complete Freund's adjuvant (inflammatory group: n = 8) was applied to the disc. Seven days after the second operation, T13-L5 dorsal root ganglions were processed for double staining of CGRP and IB4.

Results: Of the Fluoro-Gold-labeled neurons, 50.1 +/- 4.6% (mean +/- SEM) were positive for CGRP and 0.7 +/- 0.6% positive for IB4 in the control group, while 65.6 +/- 4.7% were positive for CGRP and 1.0 +/- 1.0% positive for IB4 in the inflammatory group. The percentage of CGRP-ir neurons was significantly higher than that of IB4-binding neurons in both groups (P < 0.001, each). The percentage of CGRP-ir neurons in the inflammatory group was significantly higher than in the control group (P < 0.05).

Conclusions: We found that most small neurons innervating the disc were CGRP-ir. Furthermore, disc inflammation caused an increase in CGRP-ir neurons but not IB4-binding neurons, suggesting that CGRP-ir, nerve growth factor-dependent neurons are more responsible for discogenic pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport
  • Calcitonin Gene-Related Peptide / analysis*
  • Cell Size
  • Coloring Agents
  • Discitis / physiopathology*
  • Fluorescent Dyes
  • Ganglia, Spinal / cytology*
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glycoproteins / analysis*
  • Intervertebral Disc / innervation*
  • Lectins / analysis*
  • Lumbar Vertebrae*
  • Male
  • Nerve Growth Factors / physiology*
  • Neuralgia / physiopathology*
  • Neurons, Afferent / chemistry
  • Neurons, Afferent / classification
  • Neurons, Afferent / ultrastructure*
  • Plant Lectins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nerve Growth Factor / physiology*
  • Sciatica / physiopathology
  • Stilbamidines
  • Versicans

Substances

  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Coloring Agents
  • Fluorescent Dyes
  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glycoproteins
  • Griffonia simplicifolia lectins
  • Lectins
  • Nerve Growth Factors
  • Plant Lectins
  • Receptors, Nerve Growth Factor
  • Stilbamidines
  • Vcan protein, rat
  • Versicans
  • Calcitonin Gene-Related Peptide