Sensory and autonomic innervation of the cervical intervertebral disc in rats: the pathomechanics of chronic discogenic neck pain

Spine (Phila Pa 1976). 2012 Jul 15;37(16):1357-62. doi: 10.1097/BRS.0b013e31824ba710.

Abstract

Study design: An immunohistological analysis of the cervical intervertebral disc (IVD).

Objective: To investigate sensory and autonomic innervation of the rat cervical IVD.

Summary of background data: Many clinicians are challenged with treating wide-ranging chronic neck pain. Several authors have reported that sympathetic nerves participate in chronic pain, and various sympathectomy procedures can effectively treat chronic pain.

Methods: The neuro-tracer Fluoro-gold (FG) was applied to the anterior surfaces of C5-C6 IVDs from 10 Sprague-Dawley rats to label the neurons of the innervating dorsal root ganglion (DRG), stellate ganglion (SG; sympathetic ganglion), and nodose ganglion (NG; parasympathetic ganglion). Seven days postsurgery, DRGs from level C1-C8, SG, and NG neurons were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP; a marker for peptide-containing neurons) and isolectin B4 (IB4; a marker for nonpeptide-containing neurons). The proportion of FG-labeled DRG neurons that were CGRP-immunoreactive (CGRP-IR), IB4-binding, and non-CGRP-IR and IB4-binding, and the proportion of FG-labeled SG neurons and NG neurons were calculated.

Results: FG-labeled neurons innervating the C5-C6 IVD were distributed throughout the C2-C8 DRGs. The proportions of FG-labeled DRG neurons that were CGRP-IR, IB4-binding, non-CGRP-IR and IB4-binding, as well as SG neurons, and NG neurons were 20.6%, 3.3%, 55.7%, 8.9%, and 11.5%, respectively. The proportion of CGRP-IR FG-labeled DRG neurons was significantly higher than the proportion of IB4-binding FG-labeled DRG neurons at each level (P < 0.05).

Conclusion: The C5-C6 IVD was innervated multisegmentally from neurons of the C2-C8 DRG, SG, and NG. Overall, 79.6% of the nerve fibers innervating the IVD were sensory nerves and 20.4% were autonomic nerves. Furthermore, 23.9% of the nerve fibers innervating the IVD were afferent sensory pain-related nerves, 8.9% were efferent sympathetic nerves, and 11.5% were efferent parasympathetic nerves. These findings may explain the wide-ranging and chronic discogenic pain that occurs via the somatosensory and autonomic nervous system.

MeSH terms

  • Animals
  • Autonomic Pathways* / chemistry
  • Autonomic Pathways* / physiopathology
  • Biomarkers / analysis
  • Calcitonin Gene-Related Peptide / analysis
  • Cervical Vertebrae / innervation*
  • Chronic Pain / physiopathology*
  • Fluorescent Dyes
  • Immunohistochemistry
  • Intervertebral Disc / innervation*
  • Lectins / analysis
  • Male
  • Neck Pain / physiopathology*
  • Neuroanatomical Tract-Tracing Techniques
  • Neuronal Tract-Tracers
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells* / chemistry
  • Stilbamidines

Substances

  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Biomarkers
  • Fluorescent Dyes
  • Lectins
  • Neuronal Tract-Tracers
  • Stilbamidines
  • Calcitonin Gene-Related Peptide