Painful intervertebral disc degeneration is mediated by inflammation that modulates glycosylation and induces hyperinnervation and sensory sensitization, which result in discogenic pain. Hyaluronic acid (HA) used as a therapeutic biomaterial can reduce inflammation and pain, but the effects of HA therapy on glycosylation and pain associated with disc degeneration have not been previously determined. We describe a novel rat model of pain induced by intervertebral disc injury, with validation of the pain phenotype by morphine treatment. Using this model, we assessed the efficacy of HA hydrogel for the alleviation of pain, demonstrating that it reduced nociceptive behavior, an effect associated with down-regulation of nociception markers and inhibition of hyperinnervation. Furthermore, HA hydrogel altered glycosylation and modulated key inflammatory and regulatory signaling pathways, resulting in attenuation of inflammation and regulation of matrix components. Our results suggest that HA hydrogel is a promising clinical candidate for the treatment of back pain caused by degenerated discs.

中文翻译：

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透明质酸水凝胶的植入可防止大鼠椎间盘损伤模型的疼痛表型。

椎间盘疼痛的恶化是由炎症介导的，该炎症调节糖基化并诱导神经过度支配和感觉敏化，从而导致椎间盘源性疼痛。用作治疗性生物材料的透明质酸（HA）可以减轻炎症和疼痛，但是先前尚未确定HA治疗对与椎间盘退变相关的糖基化和疼痛的影响。我们描述了一种新型的大鼠椎间盘损伤所致疼痛的大鼠模型，并通过吗啡治疗验证了疼痛表型。使用该模型，我们评估了HA水凝胶缓解疼痛的功效，证明其降低了伤害感受行为，与伤害感受标记的下调和过度神经支配抑制相关的作用。此外，HA水凝胶改变了糖基化并调节了关键的炎症和调节信号通路，导致炎症减弱和基质成分的调节。我们的结果表明，HA水凝胶是用于治疗由椎间盘退变引起的背痛的有前途的临床候选药物。