经典高分文献阅读·疼痛与治疗－口服阿片类药物对中度至重度癌痛患者炎症细胞因子和肠道菌群的影响

Clinical Observation of the Effects of Oral Opioid on Inflammatory Cytokines and Gut Microbiota in Patients with Moderate to Severe Cancer Pain： A Retrospective Cohort Study口服阿片类药物对中度至重度癌痛患者炎症细胞因子和肠道菌群影响的临床观察：一项回顾性队列研究

ABSTRACT

Introduction

Recent studies have revealed that inflammation is a key factor in the causation of opioid analgesic tolerance． Opioids can induce a massive release of inflammatory cytokines and disruption of intestinal barrier function by activating Toll－like receptors 2／4 （TLR2／4）， eventually resulting to sustained bacterial transmission and persistent systemic inflammation． However， most of the relevant analyses available were conducted at the level of animal experiments． It is necessary to explore the potential association between opioid tolerance and inflammatory cytokines and gut microbiota in patients with cancer pain．

介绍

最近的研究表明，炎症是导致阿片类镇痛耐受性的关键因素。阿片类药物可通过激活 Toll 样受体 2／4 （TLR2／4） 诱导炎症细胞因子的大量释放和肠道屏障功能的破坏，最终导致持续的细菌传播和持续的全身炎症。然而，大多数可用的相关分析都是在动物实验水平上进行的。有必要探索癌痛患者阿片类药物耐受性与炎性细胞因子和肠道微生物群之间的潜在关联。

Methods

We retrospectively analyzed cytokines， lymphocyte subsets and blood cells in 186 cancer patients to examine the effect of oral opioids on inflammatory cytokines in patients with moderate to severe cancer pain． The control group constituted tumor patients without cancer pain， while patients with moderate to severe cancer pain taking oral opioids made up the observation group． Fecal samples collected from 25 cancer patients were also analyzed for the composition and diversity of gut microbiota using 16S rRNA sequencing to explore the association between oral opioids and dynamic changes in gut microbiota．

方法

我们回顾性分析了 186 名癌症患者的细胞因子、淋巴细胞亚群和血细胞，以检查口服阿片类药物对中度至重度癌症疼痛患者炎性细胞因子的影响。对照组为无癌痛的肿瘤患者，而服用口服阿片类药物的中度至重度癌痛患者为观察组。还使用 16S rRNA 测序分析了从 25 名癌症患者收集的粪便样本中肠道菌群的组成和多样性，以探索口服阿片类药物与肠道菌群动态变化之间的关联。

Results

Patients with moderate to severe cancer pain taking oxycodone had significantly higher levels of IL－2， IL－4， IL－6， IL－10， TNF－α， and IFN－γ than those in the control group （p ＜ 0．001）． The difference in the relative abundance of Lactobacillus （p ＝ 0．025）， Anaerostipes （p ＝ 0．034）， Megamonas （p ＝ 0．0080）， Monoglobus （p ＝ 0．0080）， and the Rikenellaceae＿RC9＿gut＿group （p ＝ 0．022） between the opioid and control group was significant．

结果

服用羟考酮的中重度癌痛患者的IL－2、IL－4、IL－6、IL－10、TNF－α和IFN－γ水平显着高于对照组（p  ＜0．001）。阿片类药物组与对照组的乳酸杆菌 （ p  ＝ 0．025）、厌氧菌属 （ p  ＝ 0．034）、巨单胞菌属 （ p  ＝ 0．0080）、单球菌属 （ p  ＝ 0．0080） 和 Rikenellaceae＿RC9＿gut＿group （ p  ＝ 0．022）的相对丰度差异为重大。

Conclusion

Oral oxycodone can cause abnormal changes in cytokine levels and gut microbiota of patients with moderate to severe cancer pain， prompting chronic systemic inflammation． Analgesic tolerance induced by long－term oxycodone use could be closely related to the consistent upregulation of IL－6 and TNF－α levels．

结论

口服羟考酮可导致中度至重度癌痛患者的细胞因子水平和肠道菌群发生异常变化，引发慢性全身炎症。长期使用羟考酮诱导的镇痛耐受性可能与 IL－6 和 TNF－α 水平的持续上调密切相关。

Key Summary Points

Why carry out this study？

ü Recent studies have revealed that inflammation is a key factor in the causation of opioid analgesic tolerance． Opioids can induce a massive release of inflammatory cytokines and disruption of intestinal barrier function by activating TLR2／4， eventually resulting to sustained bacterial transmission and persistent systemic inflammation．

ü Most of the relevant analyses available were conducted at the level of animal experiments． It is necessary to explore the potential association between opioid tolerance and inflammatory cytokines and gut microbiota in patients with cancer pain．

为什么要开展这项研究？

ü 最近的研究表明，炎症是导致阿片类镇痛耐受性的关键因素。阿片类药物可通过激活 TLR2／4 诱导炎症细胞因子的大量释放和肠道屏障功能的破坏，最终导致持续的细菌传播和持续的全身炎症。

ü 大多数可用的相关分析都是在动物实验水平上进行的。有必要探索癌痛患者阿片类药物耐受性与炎性细胞因子和肠道微生物群之间的潜在关联。

What was learned from the study？

ü Oral oxycodone can cause abnormal alterations in body inflammatory cytokine levels and gut microbiota of patients with moderate to severe cancer pain， promoting chronic systemic inflammation．

ü Analgesic tolerance induced by long－term oxycodone use may be closely related to the consistent upregulation of IL－6 and TNF－α levels．

从研究中学到了什么？

ü 口服羟考酮可引起中度至重度癌痛患者体内炎症细胞因子水平和肠道菌群的异常改变，促进慢性全身炎症。

ü 长期使用羟考酮诱导的镇痛耐受性可能与 IL－6 和 TNF－α 水平的持续上调密切相关。

翻译：riozhou

排版：肉肉

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