慢性肌肉骨骼疼痛处方阿片类药物使用者的OPRM1 DNA甲基化特征

IF 3.4 Q2 NEUROSCIENCES Pain Reports Pub Date : 2022-11-01 DOI:10.1097/PR9.0000000000001046

Sophia Sheikh, Carmen Smotherman, Monika Patel, Taimour Langaee, Danxin Wang, Edward Swaray, Esteban Velasquez, Siegfried O F Schmidt, Phyllis Hendry, Larisa H Cavallari, Roger B Fillingim

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Epigenetic modification of the μ-opioid receptor 1 (OPRM1) gene, which codes for the target protein of opioids, may influence vulnerability to opioid abuse and response to opioid pharmacotherapy, potentially affecting pain outcomes.Objective: Our objective was to investigate associations of clinical and sociodemographic factors with OPRM1 DNA methylation in patients with chronic musculoskeletal pain on long-term prescription opioids.Methods: Sociodemographic variables, survey data (Rapid Estimate of Adult Health Literacy in Medicine-Short Form, Functional Comorbidity Index [FCI], PROMIS 43v2.1 Profile, Opioid Risk Tool, and PROMIS Prescription Pain Medication Misuse), and saliva samples were collected. The genomic DNA extracted from saliva samples were bisulfite converted, amplified by polymerase chain reaction, and processed for OPRM1-targeted DNA methylation analysis on a Pyrosequencing instrument (Qiagen Inc, Valencia, CA). 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引用次数: 1

摘要

许多慢性疼痛患者使用处方阿片类药物。μ-阿片受体1 (OPRM1)基因编码阿片样物质的靶蛋白，其表观遗传修饰可能影响对阿片样物质滥用的易感性和对阿片样物质药物治疗的反应，可能影响疼痛结局。目的:我们的目的是研究长期服用处方阿片类药物的慢性肌肉骨骼疼痛患者的临床和社会人口因素与OPRM1 DNA甲基化的关系。方法:收集社会人口学变量、调查数据(成人医学健康素养快速评估简表、功能共病指数[FCI]、PROMIS 43v2.1简介、阿片类药物风险工具和PROMIS处方止痛药滥用)和唾液样本。从唾液样本中提取的基因组DNA被亚硫酸转化，通过聚合酶链反应扩增，并在焦磷酸测序仪器(Qiagen Inc .， Valencia, CA)上进行oprm1靶向DNA甲基化分析。使用一般线性模型来检查预测因子与OPRM1 DNA甲基化之间的关系。结果:对112例患者资料进行分析。最佳拟合的多变量模型显示，与对照组相比，阅读水平> 8年级、椎间盘退行性疾病、药物滥用合并症和阿片类药物使用< 1年(>5年)的患者的平均甲基化水平分别比参照组高7.7%(95%置信区间[CI] 0.95%， 14.4%)、11.7% (95% CI 2.7%， 21.1%)、21.7% (95% CI 10.7%， 32.5%)和16.1% (95% CI 3.3%， 28.8%)。FCI每增加1个单位，甲基化水平降低2.2% (95% CI 0.64%， 3.7%)，疲劳T评分每增加一个单位，甲基化水平升高0.45% (95% CI 0.08%， 0.82%)。结论:OPRM1甲基化水平受多种患者因素影响。需要进一步的研究来重复这些发现并确定潜在的临床应用。

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Characterizing OPRM1 DNA methylation in prescription opioid users with chronic musculoskeletal pain.

Introduction: Many patients with chronic pain use prescription opioids. Epigenetic modification of the μ-opioid receptor 1 (OPRM1) gene, which codes for the target protein of opioids, may influence vulnerability to opioid abuse and response to opioid pharmacotherapy, potentially affecting pain outcomes.

Objective: Our objective was to investigate associations of clinical and sociodemographic factors with OPRM1 DNA methylation in patients with chronic musculoskeletal pain on long-term prescription opioids.

Methods: Sociodemographic variables, survey data (Rapid Estimate of Adult Health Literacy in Medicine-Short Form, Functional Comorbidity Index [FCI], PROMIS 43v2.1 Profile, Opioid Risk Tool, and PROMIS Prescription Pain Medication Misuse), and saliva samples were collected. The genomic DNA extracted from saliva samples were bisulfite converted, amplified by polymerase chain reaction, and processed for OPRM1-targeted DNA methylation analysis on a Pyrosequencing instrument (Qiagen Inc, Valencia, CA). General linear models were used to examine the relationships between the predictors and OPRM1 DNA methylation.

Results: Data from 112 patients were analyzed. The best-fitted multivariable model indicated, compared with their counterparts, patients with > eighth grade reading level, degenerative disk disease, substance abuse comorbidity, and opioid use < 1 year (compared with >5 years), had average methylation levels that were 7.7% (95% confidence interval [CI] 0.95%, 14.4%), 11.7% (95% CI 2.7%, 21.1%), 21.7% (95% CI 10.7%, 32.5%), and 16.1% (95% CI 3.3%, 28.8%) higher than the reference groups, respectively. Methylation levels were 2.2% (95% CI 0.64%, 3.7%) lower for every 1 unit increase in FCI and greater by 0.45% (95% CI 0.08%, 0.82%) for every fatigue T score unit increase.

Conclusions: OPRM1 methylation levels varied by several patient factors. Further studies are warranted to replicate these findings and determine potential clinical utility.

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