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


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


BACKGROUND
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.
Aoki
Yasuchika
Y
Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. yasuaoki@h6.dion.ne.jp
Ohtori
Seiji
S
Ino
Hidetoshi
H
Douya
Hideo
H
Ozawa
Tomoyuki
T
Saito
Tomoko
T
Moriya
Hideshige
H
Takahashi
Kazuhisa
K
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D015299:Discitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000494:pharmacology; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D007403:Intervertebral Disc / Q000187:drug effects / Q000294:innervation*; D008159:Lumbar Vertebrae; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013266:Stilbamidines / Q000378:metabolism
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D015415:Biomarkers; D019922:GAP-43 Protein; D013266:Stilbamidines; D005620:Freund's Adjuvant; D015740:Calcitonin Gene-Related Peptide