Direct Application of the Tumor Necrosis Factor-α Inhibitor, Etanercept, Into a Punctured Intervertebral Disc Decreases Calcitonin Gene-Related Peptide Expression in Rat Dorsal Root Ganglion Neurons

被引：41

作者：

Horii, Manato ^{[1
]}

Orita, Sumihisa ^{[1
]}

Nagata, Maiko ^{[1
]}

Takaso, Masashi ^{[1
]}

Yamauchi, Kazuyo ^{[1
]}

Yamashita, Masaomi ^{[1
]}

Inoue, Gen ^{[1
]}

Eguchi, Yawara ^{[1
]}

Ochiai, Nobuyasu ^{[1
]}

Kishida, Shunji ^{[1
]}

Aoki, Yasuchika ^{[1
]}

Ishikawa, Tetsuhiro ^{[1
]}

Arai, Gen ^{[1
]}

Miyagi, Masayuki ^{[1
]}

Kamoda, Hiroto ^{[1
]}

Kuniyoshi, Kazuki ^{[1
]}

Suzuk, Miyako ^{[1
]}

Nakamura, Junichi ^{[1
]}

Toyone, Tomoaki ^{[1
]}

Takahashi, Kazuhisa ^{[1
]}

Ohtori, Seiji ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Orthopaed Surg, Chuo Ku, Chiba 2608670, Japan

来源：

SPINE | 2011年 / 36卷 / 02期

关键词：

etanercept; intervertebral disc; lumbar; tumor necrosis factor-alpha; calcitonin gene-related peptide; LUMBAR FACET JOINTS; NUCLEUS PULPOSUS; SUBSTANCE-P; BACK-PAIN; SENSORY INNERVATION; INFLAMMATION; REGENERATION; INVOLVEMENT; MECHANISMS; CYTOKINES;

D O I：

10.1097/BRS.0b013e3181d4be3c

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Study Design. Retrograde neurotracing and immunohistochemistry were used to investigate the effect of the tumor necrosis factor (TNF)-alpha inhibitor, etanercept, on calcitonin gene-related peptide (CGRP) expression in dorsal root ganglion (DRG) neurons innervating intervertebral discs in rats. Objective. To clarify the action of a TNF-alpha inhibitor on a sensory neuropeptide in DRG neurons innervating intervertebral discs. Summary of Background Data. Degeneration of lumbar intervertebral discs is a cause of low back pain. TNF-alpha in the intervertebral disc is a major contributor to discogenie pain. Effects of TNF-alpha inhibition on CGRP expression in DRG neurons were evaluated. Methods. The neurotracer FluoroGold was applied to the surfaces of L4/5 discs to label their innervating DRG neurons (n = 30). Of 30 rats, 10 were in a nonpunctured disc sham surgery control group, whereas the other 20 were in experimental groups in which intervertebral discs were punctured with a 23-gauge needle. Etanercept or saline was applied into the punctured discs (n = 10 each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for CGRP. The proportion of FluoroGold-labeled CGRP-immunoreactive DRG neurons was evaluated in all groups. Results. FluoroGold-labeled neurons innervating the L4/5 disc were distributed throughout L1-L6 DRGs in all groups. Of the FluoroGold-labeled neurons, the proportion of CGRP-immunoreactive neurons was 21% +/- 4% in the sham surgery control group, 32% +/- 7% in the puncture + saline group, and 23% +/- 4% in the puncture + etanercept group. The proportion of CGRP-immunoreactive neurons was significantly greater in the puncture + saline group compared with the sham control and puncture + etanercept groups (P < 0.01). Conclusion. In this model, CGRP was upregulated in DRG neurons innervating damaged discs. However, direct intradiscal application of etanercept immediately after disc puncture suppressed CGRP expression in DRG neurons innervating injured discs. This finding may further elucidate the mechanism for the effectiveness of etanercept in upregulation of neuropeptide in DRG neurons innervating intervertebral discs.

引用

页码：E80 / E85

页数：6

共 25 条

[1]

[Anonymous], 1970, J JPN ORTHOP ASS

[2]

Expression and co-expression of VR1, CGRP, and IB4-binding glycoprotein in dorsal root ganglion neurons in rats: Differences between the disc afferents and the cutaneous afferents [J].