The Red Wine Polyphenol Resveratrol Shows Promising Potential for the Treatment of Nucleus Pulposus–Mediated Pain In Vitro and In Vivo

Wuertz, Karin; Quero, Lilian; Sekiguchi, Miho; Klawitter, Marina; Nerlich, Andreas G.; Konno, Satoshi; Kikuchi, Shinichi; Boos, Norbert

doi:10.1097/brs.0b013e318221e655

Cited by 86 publications

(83 citation statements)

References 40 publications

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“…Resveratrol, a naturally occurring polyphenol present in red wine, was able to reduce IL-6, IL-8, MMP1, MMP3 and MMP13 expression when injected into the IVD [170]. Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), an anthraquinone molecule derived from the rhizome of Rheum palmatum that exhibits anti-inflammatory activity and is used in the treatment of osteoarthritis and pain relief, was hypothesized to be a therapeutic agent for IVD through the regulation of IL-1 activity [171].…”

Section: Injection Of Moleculesmentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

325

256

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Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players.

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Section: Injection Of Moleculesmentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

325

256

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“…The gram ratings for von Frey hairs were based on the ratings supplied by the manufacturer. The filaments were sequentially applied to the paw surface just until the filament bent and was held for 3 s. The response was considered positive if the rat lifted the foot in combination with either licking or shaking of the foot as an escape response (Kobayashi et al, 2011;Wuertz et al, 2011).…”

Section: In Vivo Study On Pain Behaviourmentioning

confidence: 99%

“…Animals from the NP application group were divided into four groups (n = 12 in each): NP + EGCG 10 µM (0.1 mL of 10 µM EGCG), NP + EGCG 100 µM (0.1 mL of 100 µM EGCG), NP + water (0.1 mL of water as a vehicle), and NP (non-treatment) group. Animals in the treatment groups were injected with 0.1 mL of the designed treatment solution into the underlayer of epineurium, just distal to the NP, before closing the incisions (Kobayashi et al, 2011;Wuertz et al, 2011). Sensitivity to non-noxious mechanical stimuli was tested using the von Frey Filament test.…”

Section: In Vivo Study On Pain Behaviourmentioning

confidence: 99%

“…Recently, tissueengineered IVDs that formed a functional motion segment were used to replace the degenerated discs in rodent caudal spine (Bowles et al, 2011) and chemical crosslinking was applied to stabilise the AF tissue in vitro (Hedman et al, 2006). Anti-inflammatory and anti-catabolic substances that target the metabolism and inflammatory signalling within the IVD also represent a new, interesting treatment option (Klawitter et al, 2012a;Klawitter et al, 2012b;Sinclair et al, 2011;Wuertz et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats

Krupková¹,

Sekiguchi²,

Klasen³

et al. 2014

eCM

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Intervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in Sprague-Dawley rats (n = 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-B. AbstractIntervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1β, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in SpragueDawley rats (n = 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB.

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“…Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-a), Interleukin-1-beta (IL-1b), Interleukin-6 (IL-6), and nitric oxide, phospholipase A2, and serotonin, are known chemical inducers of sciatica [1,3,13,14,17,18,22,32]. Nucleus pulposus contains TNF-a, and nucleus pulposus applied to the dorsal root ganglion (DRG) induces pain-related behavior in rats and causes morphological and functional changes in DRG and spinal cord [13,14,26,29,30,32,37,48].…”

Section: Introductionmentioning

confidence: 99%

The effect of selective serotonin reuptake inhibitor (SSRI) on pain-related behavior in a rat model of neuropathic pain

et al. 2014

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Introduction Some antidepressants are effective for treating neuropathic pain independent of any effect on depression. Selective serotonin reuptake inhibitors (SSRIs) are one of the potential agents to treat neuropathic pain. The aims of this study were to compare the effects of SSRI and non-steroidal anti-inflammatory drugs (NSAIDs) on pain-related behavior and expression of cytokines in a rat model of neuropathic pain. Materials and methods Spinal surgery was performed to apply nucleus pulposus (NP) to the dorsal root ganglion (DRG). NP animals were treated with saline (NP ? S

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The Red Wine Polyphenol Resveratrol Shows Promising Potential for the Treatment of Nucleus Pulposus–Mediated Pain In Vitro and In Vivo

Cited by 86 publications

References 40 publications

Inflammation in intervertebral disc degeneration and regeneration

Inflammation in intervertebral disc degeneration and regeneration

Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats

The effect of selective serotonin reuptake inhibitor (SSRI) on pain-related behavior in a rat model of neuropathic pain

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