Sensory and autonomic innervation of the cervical intervertebral disc in rats: the pathomechanics of chronic discogenic neck pain.
METHODS
An immunohistological analysis of the cervical intervertebral disc (IVD).


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


BACKGROUND
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).


CONCLUSIONS
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.
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kazuki
K
Fujimoto
Masayuki
M
Miyagi
Tetsuhiro
T
Ishikawa
Gen
G
Inoue
Yawara
Y
Eguchi
Hiroto
H
Kamoda
Gen
G
Arai
Miyako
M
Suzuki
Sumihisa
S
Orita
Gou
G
Kubota
Yoshihiro
Y
Sakuma
Yasuhiro
Y
Oikawa
Kazuki
K
Kuniyoshi
Nobuyasu
N
Ochiai
Shunji
S
Kishida
Junichi
J
Nakamura
Yasuchika
Y
Aoki
Tomoaki
T
Toyone
Kazuhisa
K
Takahashi
Seiji
S
Ohtori
D000818:Animals; D017776:Autonomic Pathways / Q000737:chemistry / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D002574:Cervical Vertebrae / Q000294:innervation*; D059350:Chronic Pain / Q000503:physiopathology*; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000294:innervation*; D037102:Lectins / Q000032:analysis; D008297:Male; D019547:Neck Pain / Q000503:physiopathology*; D056347:Neuroanatomical Tract-Tracing Techniques; D056325:Neuronal Tract-Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000737:chemistry; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D015415:Biomarkers; D005456:Fluorescent Dyes; D037102:Lectins; D056325:Neuronal Tract-Tracers; D013266:Stilbamidines; D015740:Calcitonin Gene-Related Peptide