Dietary polyphenols as a safe and novel intervention for modulating pain associated with intervertebral disc degeneration in an in-vivo rat model

Abstract

Developing effective therapies for back pain associated with intervertebral disc (IVD) degeneration is a research priority since it is a major socioeconomic burden and current conservative and surgical treatments have limited success. Polyphenols are naturally occurring compounds in plant-derived foods and beverages, and evidence suggests dietary supplementation with select polyphenol preparations can modulate diverse neurological and painful disorders. This study tested whether supplementation with a select standardized Bioactive-Dietary-Polyphenol-Preparation (BDPP) may alleviate pain symptoms associated with IVD degeneration. Painful IVD degeneration was surgically induced in skeletally-mature rats by intradiscal saline injection into three consecutive lumbar IVDs. Injured rats were given normal or BDPP-supplemented drinking water. In-vivo hindpaw mechanical allodynia and IVD height were assessed weekly for 6 weeks following injury. Spinal column, dorsal-root-ganglion (DRG) and serum were collected at 1 and 6 weeks post-operative (post-op) for analyses of IVD-related mechanical and biological pathogenic processes. Dietary BDPP significantly alleviated the typical behavioral sensitivity associated with surgical procedures and IVD degeneration, but did not modulate IVD degeneration nor changes of pro-inflammatory cytokine levels in IVD. Gene expression analyses suggested BDPP might have an immunomodulatory effect in attenuating the expression of pro-inflammatory cytokines in DRGs. This study supports the idea that dietary supplementation with BDPP has potential to alleviate IVD degeneration-related pain, and further investigations are warranted to identify the mechanisms of action of dietary BDPP.

Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section

“…On the other hand, the safranin‐O stains proteoglycans, chondrocytes and type II collagen red, while the fast‐green counterstains the non‐collagen components and provides a clear contrast to the safranin‐O staining. The two stainings can be performed on separate sections, or for simplicity, hematoxylin can be combined sequentially with SO/FG staining in single section (ie, safranin‐O/fast‐green/hematoxylin) 5,7,13 …”

“…Both rat lumbar and coccygeal IVDs are structurally, morphologically and biochemically comparable with human IVDs, and are commonly used for studying IVD degeneration 2‐5 . Similar to human IVDs, the rat degenerated IVDs exhibited decreased NP volume, reduced NP cellularity, ruptured and disorganized AF, and a shift towards catabolism with reduced extracellular matrix production and increased matrix degrading enzymes and pro‐inflammatory cytokines 5,7,12‐23 . However, it should be noted that large vacuolated notochordal cells occupy the NP of skeletally mature rat IVDs, 37 while this phenotypic differentiation in humans occurs before skeletal maturity in human IVDs.…”

“…Despite being relatively small subjects, rats can still be used for multiple surgical procedures, including annular puncture, and intradiscal injection 2‐11 . Rat IVD degeneration models are particularly important since they enable the measurement of pain‐associated behaviors due to well‐established behavioral assays 7,12‐17 . Moreover, the rat model is a useful preclinical tool for determining the efficacies and mechanisms of experimental therapeutic interventions for both IVD degeneration and discogenic pain.…”

“…[2][3][4][5][6][7][8][9][10][11] Rat IVD degeneration models are particularly important since they enable the measurement of pain-associated behaviors due to well-established behavioral assays. 7,[12][13][14][15][16][17] Moreover, the rat model is a useful preclinical tool for determining the efficacies and mechanisms of experimental therapeutic interventions for both IVD degeneration and discogenic pain.…”

Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions

“…Dietary supplementation of grape polyphenol, which contained resveratrol, to rats with punctured discs reduced the behavioral sensitivity and gene expression levels of proinflammatory cytokines in DRGs but failed to alleviate disc degeneration or change the proinflammatory cytokine level in IVD. 164 In vitro, resveratrol partially counteracted the inflammatory effects of TNF-α and IL-1β, including decreased ECM content and increased NP cell senescence and matrix degradation enzymes (MMP-3, MMP-13, and ADAMTS-4). 165 Resveratrol also showed a similar anticatabolic effect to reverse the matrix degradation and apoptotic induction of oxidative damage caused by hydrogen peroxide in NP cells.…”