Moh Edward S X, Nishtala Krishnatej, Iqbal Sameera, Staikopoulos Vasiliki, Kapur Dilip, Hutchinson Mark R, Packer Nicolle H
ARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, New South Wales, 2109, Australia.
Department of Molecular Science, Macquarie University, Sydney, New South Wales, 2109, Australia.
Glycobiology. 2022 Feb 26;32(1):50-59. doi: 10.1093/glycob/cwab098.
Opioid use for treatment of persistent pain has increased dramatically over the past two decades, but it has not resulted in improved pain management outcomes. To understand the molecular mechanisms of opioids, molecular signatures that arise from opioid exposure are often sought after, using various analytical methods. In this study, we performed proteomics, and multiglycomics via sequential analysis of polysialic acids, glycosaminoglycans, N-glycans and O-glycans, using the same cerebral spinal fluid (CSF) sample from patients that had long-term (>2 years), intrathecal morphine or baclofen administered via an indwelling pump. Proteomics and N-glycomics signatures between the two treatment groups were highly conserved, while significant differences were observed in polysialic acid, heparan sulfate glycosaminoglycan and O-glycan profiles between the two treatment groups. This represents the first study to investigate the potential relationships between diverse CSF conjugated glycans and long-term intrathecal drug exposure. The unique changes, observed by a sequential analytical workflow, reflect previously undescribed molecular effects of opioid administration and pain management.
在过去二十年中，用于治疗持续性疼痛的阿片类药物使用量急剧增加，但并未改善疼痛管理效果。为了了解阿片类药物的分子机制，人们经常使用各种分析方法来寻找因接触阿片类药物而产生的分子特征。在本研究中，我们对长期（>2年）通过留置泵鞘内注射吗啡或巴氯芬的患者的同一脑脊液（CSF）样本进行了蛋白质组学和多聚糖组学分析，后者通过对多唾液酸、糖胺聚糖、N-聚糖和O-聚糖的顺序分析来实现。两个治疗组之间的蛋白质组学和N-聚糖特征高度保守，而在两个治疗组之间观察到多唾液酸、硫酸乙酰肝素糖胺聚糖和O-聚糖谱存在显著差异。这是第一项研究不同脑脊液结合聚糖与长期鞘内药物暴露之间潜在关系的研究。通过顺序分析工作流程观察到的独特变化反映了阿片类药物给药和疼痛管理之前未被描述的分子效应。
