Upregulation of NaV1.7 in dorsal root ganglia after intervertebral disc injury in rats.
METHODS
Animal study.


OBJECTIVE
To investigate pain-related expression of NaV1.7 in dorsal root ganglia (DRG) innervating intervertebral discs.


BACKGROUND
The pathophysiology of discogenic low back pain is not fully understood. Prostaglandins and cytokines produced by degenerated discs can cause pain, but nonsteroidal anti-inflammatory and steroid medications are often ineffective at pain reduction. Tetrodotoxin-sensitive, voltage-gated sodium (NaV) channels are associated with sensory transmission in primary sensory nerves, and the NaV1.7 channel has emerged as an attractive analgesic target. The purpose of this study was to investigate pain-related expression of NaV1.7 in DRG innervating intervertebral discs.


METHODS
Using a rodent model of disc puncture, we labeled DRG neurons innervating L5-L6 discs with FluoroGold neurotracer (n = 20). Half of the rats (n = 10) underwent intervertebral disc puncture using a 23-gauge needle (puncture group), and the other half underwent non-puncture sham surgery (non-puncture group). Seven and 14 days after surgery, DRGs from the L1 to L6 levels were harvested, sectioned, and immunostained for NaV1.7, and the proportion of NaV1.7-immunoreactive DRG neurons was evaluated.


RESULTS
NaV1.7 was expressed in DRG neurons innervating intervertebral discs from L1 to L5. The ratio of NaV1.7-expressing DRG neurons to total FG-labeled neurons was 7.2% and 7.6% at 1 and 2 weeks after surgery, respectively, in the non-puncture group and 16.2% and 16.3% at 1 and 2 weeks, respectively, in the puncture group. The upregulation of NaV1.7 after puncture was significant at both 1 and 2 weeks after surgery (P < 0.01).


CONCLUSIONS
We found that disc injury increases NaV1.7 expression in DRG neurons innervating injured discs. NaV1.7 may be a therapeutic target for pain control in patients with lumbar disc degeneration.
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Aya
A
Sadamasu
Yoshihiro
Y
Sakuma
Miyako
M
Suzuki
Sumihisa
S
Orita
Kazuyo
K
Yamauchi
Gen
G
Inoue
Yasuchika
Y
Aoki
Tetsuhiro
T
Ishikawa
Masayuki
M
Miyagi
Hiroto
H
Kamoda
Gou
G
Kubota
Yasuhiro
Y
Oikawa
Kazuhide
K
Inage
Takeshi
T
Sainoh
Jun
J
Sato
Junichi
J
Nakamura
Tomoaki
T
Toyone
Kazuhisa
K
Takahashi
Seiji
S
Ohtori
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000293:injuries*; D007403:Intervertebral Disc / Q000293:injuries*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000293:injuries; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
D062556:NAV1.7 Voltage-Gated Sodium Channel; C503480:Scn9a protein, rat; D015740:Calcitonin Gene-Related Peptide