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

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.针对椎间盘（intervertebral disc, IVD）退变相关腰痛开发有效治疗方案是当前的研究重点，因为该病症会造成沉重的社会经济负担，且目前的保守治疗与手术疗法的疗效均较为有限。多酚是植物源食品与饮品中天然存在的化合物，已有研究证据表明，选择性补充特定多酚制剂可调节多种神经功能障碍与疼痛性疾病。本研究旨在探究标准化活性膳食多酚制剂（Bioactive-Dietary-Polyphenol-Preparation, BDPP）的膳食补充是否能够缓解椎间盘退变相关的疼痛症状。研究通过向骨骼发育成熟的大鼠连续3个腰椎椎间盘内注射生理盐水，手术构建疼痛性椎间盘退变模型；造模成功的大鼠被给予正常饮用水或添加BDPP的饮用水。在造模后的6周内，每周对大鼠的在体后爪机械性痛觉超敏与椎间盘高度进行检测评估。分别在术后1周与6周采集大鼠的脊柱、背根神经节（dorsal-root-ganglion, DRG）与血清样本，用于分析椎间盘退变相关的力学与生物学致病过程。膳食补充BDPP可显著缓解手术造模与椎间盘退变引发的典型行为性痛觉敏感，但并未对椎间盘退变进程或椎间盘内促炎细胞因子水平的变化产生调节作用。基因表达分析结果显示，BDPP或可通过免疫调节作用降低背根神经节内促炎细胞因子的表达水平。本研究证实，膳食补充BDPP具有缓解椎间盘退变相关疼痛的应用潜力，后续仍需开展进一步研究以明确BDPP的具体作用机制。