Direct Evidence for Sensory Innervation of the Dorsal Portion of the Co5/6 Coccygeal Intervertebral Disc in Rats

Orita, Sumihisa; Ohtori, Seiji; Taniguchi, Aya; Yamashita, Masaomi; Yamauchi, Kazuyo; Inoue, Gen; Suzuki, Mitsuaki; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Takaso, Masashi; Aoki, Yasuchika; Takahashi, Kazuhisa; Kawakami, Mamoru

doi:10.1097/brs.0b013e3181c099b0

Cited by 7 publications

(6 citation statements)

References 21 publications

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“…As such these studies will need to be followed up by appropriate in vivo studies. Rat-tail IVD would appear to be a good model system for both in vitro and in vivo studies [31,32]. We believe that the data in this study support further investigation of the potential of NGF-targeted therapy in the management of IVD disease [6,33].…”

Section: Discussionsupporting

confidence: 56%

Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression

et al. 2014

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Purpose Nerve growth factor (NGF) expression and activity is important in chronic lower back pain but may also act as a pro-catabolic factor in the pathogenesis of intervertebral disc (IVD) degeneration. Lipocalin 2 (Lcn2) expression in IVD was upregulated by NGF stimulation in our previous study. The current study was undertaken to identify potential mechanisms of the latter effect including potential interactions between Lcn2 and matrix metalloproteinase 9 (MMP9). Methods Rat annulus fibrosus (AF) cells were stimulated by NGF and subjected to microarray analysis, subsequent real-time PCR, western immunoblotting, and immunofluorescence. Cells were treated with NGF in the absence or presence of the NGF inhibitor Ro 08-2750. Zymography and functional MMP9 assays were used to determine MMP9 activity, whilst the dimethyl-methylene blue assay was used to quantify the release of glycosaminoglycans (GAGs) reflecting catabolic effects following NGF treatment. Immunoprecipitation with immunoblotting was used to identify interactions between MMP9 and Lcn2. Results Increased expression of Lcn2 gene and protein following NGF stimulation was confirmed by microarray analysis, real-time PCR, western blot and immunofluorescence. Zymography showed that NGF enhanced 125-kDa gelatinase activity, identified as a Lcn2/MMP9 complex by immunoprecipitation and immunoblotting. Functional assays showed increased MMP9 activity and GAG release in the presence of NGF. The effects of NGF were neutralized by the presence of Ro 08-2750. Conclusions NGF upregulates Lcn2 expression and increases MMP9 activity in AF cells; processes which are likely to potentiate degeneration of AF tissue in vivo. Anti-NGF treatment may have benefit for management of pain Electronic supplementary material The online version of this article

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Section: Discussionsupporting

confidence: 56%

Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression

et al. 2014

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“…Retrograde FG labelling was performed as previous described 68 . Briefly, Sprague-Dawley rats were anesthetized and a dorsal longitudinal incision was made to expose the Co6-7 intervertebral disc.…”

Section: Methodsmentioning

confidence: 99%

A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain

Makino

Seki

Yahara

et al. 2017

Sci Rep

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Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

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“…The neurons innervating tail spine IVDs are mostly derived from S1 to S3 DRG. 22 The purpose of this study was to develop an IVD dynamic compression model in rats and to measure and compare infl ammatory mediators in the rat IVDs and the responses of the sensory nervous system (production of neuropeptides and markers of nerve injury and regeneration in DRG) in the newly developed IVD dynamic compression and injury model during the fi rst 8 weeks after experimental IVD dynamic compression or injury.…”

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confidence: 99%

ISSLS Prize Winner

Miyagi

Ishikawa

Kamoda

et al. 2012

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Direct Evidence for Sensory Innervation of the Dorsal Portion of the Co5/6 Coccygeal Intervertebral Disc in Rats

Cited by 7 publications

References 21 publications

Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression

Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression

A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain

ISSLS Prize Winner

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