睡眠障碍： 影响疼痛通路

本文由“小麻哥的日常”授权转载

摘要译文（供参考）

人类实验性睡眠障碍对疼痛途径的影响：中枢性疼痛抑制、环氧合酶和内源性大麻素途径

研究目的：

有强有力的证据表明，睡眠障碍是慢性疼痛的独立危险因素。

然而，这种关联的机制仍不清楚。

我们研究了实验性睡眠障碍对参与疼痛起始/缓解的三种途径的影响：（1）中枢疼痛抑制途径、（2）环氧合酶（COX）途径、（3）内源性大麻素（eCB）途径。

方法：

24名健康受试者（50%女性）按随机顺序接受了两项19天的实验室实验方案：

（a）一项实验性睡眠障碍方案，包括连续一夜的短暂睡眠和间断恢复睡眠；

（b）对照组具有8小时睡眠机会。

在整个方案中，每隔一天测量一次疼痛抑制（条件性疼痛调节、对反复疼痛的适应）、单核细胞水平的COX-2表达（LPS刺激和自发）和eCB（AEA、2-AG、DHEA、EPEA、DTEA）水平。

结果：

女性的中枢疼痛抑制通路受到睡眠障碍的影响，而男性则没有（p＜0.05条件*性别效应）。

COX-2通路（LPS刺激）被睡眠障碍激活（p＜0.05条件效应），这种效应仅由男性驱动（p＜0.01条件*性别效应）。

关于eCB途径，与对照条件相比，DHEA在睡眠障碍中更高（p＜0.05条件效应），对任何eCB没有性别差异影响。

结论：

这些发现表明，睡眠障碍可能导致慢性疼痛风险的中枢疼痛抑制COX机制是性别特异性的，这意味着需要性别差异治疗靶点来有效减少与睡眠障碍相关的慢性疼痛。

关键词：

睡眠障碍；中枢疼痛调节；环氧合酶；内源性大麻素类；疼痛机制；性别差异。

Alterations of pain pathways by experimental sleep disturbances in humans: Central pain-inhibitory, cyclooxygenase, and endocannabinoid pathways

Study objectives: 

There is strong evidence that sleep disturbances are an independent risk factor for the development of chronic pain conditions. The mechanisms underlying this association, however, are still not well understood. We examined the effect of experimental sleep disturbances on three pathways involved in pain initiation/resolution: (1) the central pain-inhibitory pathway, (2) the cyclooxygenase (COX) pathway, and (3) the endocannabinoid (eCB) pathway.

Methods: 

Twenty-four healthy participants (50% females) underwent two 19-day long in-laboratory protocols in randomized order: (a) an experimental sleep disturbance protocol consisting of repeated nights of short and disrupted sleep with intermittent recovery sleep; and  (b) a sleep control protocol consisting of nights with an 8-hour sleep opportunity.  Pain inhibition (conditioned pain modulation, habituation to repeated pain), COX-2 expression at monocyte level (LPS-stimulated and spontaneous), and eCBs (AEA, 2-AG, DHEA, EPEA, DTEA) were measured every other day throughout the protocol.

Results: 

The central pain-inhibitory pathway was compromised by sleep disturbances in females, but not in males (p<0.05 condition*sex effect). The COX-2 pathway (LPS-stimulated) was activated by sleep disturbances (p<0.05 condition effect), and this effect was exclusively driven by males (p<0.05 condition*sex effect). With respect to the eCB pathway, DHEA was higher (p<0.05 condition effect) in the sleep disturbance compared to the control condition, without sex-differential effects on any eCBs.

Conclusions: 

These findings suggest that central pain-inhibitory COX mechanisms through which sleep disturbances may contribute to chronic pain risk are sex specific, implicating the need for sex-differential therapeutic targets to effectively reduce chronic pain associated with sleep disturbances in both sexes.

Keywords: 

Sleep disturbance; central pain modulation; cyclooxygenase; endocannabinoids; pain mechanisms; sex differences.

免责声明：

文中所涉及药物使用、疾病诊疗等内容仅供医学专业人士参考。

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编辑：MiSuper.米超

校对：Michel.米萱  

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