阿片受体 μ1 基因与慢性疼痛患者接受阿片类药物治疗后的睡眠相互作用。

OPRM1 Gene Interaction with Sleep in Chronic Pain Patients Treated with Opioids.

机构信息

Pain Unit, Health Department of Alicante-General Hospital, Alicante, Spain; Neuropharmacology on Pain (NED), Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain.

Neuropharmacology on Pain (NED), Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain.

出版信息

Pain Physician. 2019 Jan;22(1):97-107.

PMID:30700073

Abstract

BACKGROUND

The experience of chronic non-cancer pain (CNCP) is one of the most common reasons individuals seek medical attention. Patients with CNCP frequently experience concomitant sleep-related problems.

OBJECTIVES

The aim was to evaluate sleep problems in opioid naïve CNCP patients, before and after opioid titration, analyzing the influence of OPRM1 gene variants.

STUDY DESIGN

A prospective, cohort, observational study.

SETTING

This study was performed at the Pain Unit of the Alicante University General Hospital.

METHODS

Pain and Medical Outcomes Study Sleep questionnaire (MOS-Sleep) were assessed at baseline and 3 months after opioid titration in 231 opioid naïve CNCP patients. Sleep data was compared with a matched-control group (n = 64). Morphine equivalent daily doses, adverse events, and drugs prescribed for pain were also registered. OPRM1 polymorphism rs1799971 was analyzed by RT-PCR. Ethics Committee approved the study and results were analyzed by R software.

RESULTS

After 3 months of opioid titration, patients with CNCP (63 ± 14 years, 64% female, VAS 74 ± 17 mm) significantly decreased pain intensity, anxiety and depression, and increased quality of life. Sleep problems were significantly more frequent in females (P = 0.002). Age, quality of life, anxiety, and depression all influenced sleep disturbances and problems indices, which were significantly different from the control group. Furthermore, the OPRM1 118-GG genotype was also associated with significantly lower sleep adequacy, and more sleep problems.

LIMITATIONS

Total number of subjects studied was relatively small and most patients were on other non-opioid centrally-acting medications.

CONCLUSIONS

Opioids decreased CNCP severity, improving patients' psychological areas, and quality of life. However, patients with OPRM1 118-GG genotype indicated an increase in sleep problems and worsening sleep pattern while taking opioids.

KEY WORDS

OPRM1, pharmacogenetics, MOS-Sleep, opioids, chronic noncancer pain, sleep related problems, sleep problem index SLP-6 and SLP-9.

摘要

背景

慢性非癌痛（CNCP）的体验是个体寻求医疗关注的最常见原因之一。CNCP 患者常伴有睡眠相关问题。

目的

评估阿片类药物初治 CNCP 患者在阿片类药物滴定前后的睡眠问题，并分析 OPRM1 基因变异的影响。

研究设计

前瞻性队列观察性研究。

地点

本研究在阿利坎特大学总医院疼痛科进行。

方法

231 例阿片类药物初治 CNCP 患者在阿片类药物滴定前和滴定后 3 个月进行疼痛和医疗结局研究睡眠问卷（MOS-Sleep）评估。将睡眠数据与匹配的对照组（n=64）进行比较。还记录了吗啡等效日剂量、不良反应和用于治疗疼痛的药物。通过 RT-PCR 分析 OPRM1 多态性 rs1799971。伦理委员会批准了该研究，结果由 R 软件进行分析。

结果

阿片类药物滴定 3 个月后，CNCP 患者（63±14 岁，64%女性，VAS 74±17mm）疼痛强度、焦虑和抑郁显著降低，生活质量提高。女性睡眠问题更常见（P=0.002）。年龄、生活质量、焦虑和抑郁均影响睡眠障碍和问题指数，与对照组有显著差异。此外，OPRM1 118-GG 基因型与睡眠充足率显著降低和更多睡眠问题相关。