Clinical measures in chronic neuropathic pain are related to the Kennedy and endocannabinoid pathways.

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2024-11-15 DOI:10.1111/eci.14351

Stephanie L Bourke, Eva Suarez Gonzalez, Barira Islam, John Stephenson, David P Finn, Patrick C McHugh

{"title":"Clinical measures in chronic neuropathic pain are related to the Kennedy and endocannabinoid pathways.","authors":"Stephanie L Bourke, Eva Suarez Gonzalez, Barira Islam, John Stephenson, David P Finn, Patrick C McHugh","doi":"10.1111/eci.14351","DOIUrl":null,"url":null,"abstract":"Background: Chronic neuropathic pain (CNP) is a debilitating condition, often refractory to currently available drugs. Understanding biochemical alterations in peripheral tissues such as blood will be useful for understanding underlying pathophysiological processes relating to CNP.Methods: We collected blood from two independent cohorts of CNP and pain-free controls (CNP n = 129/Controls n = 127) in the UK and Ireland to investigate the relationship between CNP-associated molecular/biochemical alterations and a range of clinical and pain metric parameters. Multiple statistical comparisons were conducted on the data, with selected variables included in one or more of the intended inferential analyses (six models).Results: Gene expression analysis showed that choline phosphotransferase (CHPT1) was increased (p < .001) in the CNP group compared to controls. The levels of phosphatidylcholine, a metabolite of CHPT1 in the Kennedy Pathway, were significantly (p = .008) decreased in the plasma of patients with CNP. Given the relationship between the Kennedy pathway and endocannabinoids, plasma endocannabinoids and related N-acylethanolamines were quantified in clinical samples by HPLC-Tandem Mass Spectrometry. Plasma levels of the endocannabinoid 2-arachidonoylglycerol were higher in CNP samples compared to controls, and in the statistical models applied, 2-arachidonoylglycerol significantly increased the odds of CNP (p < .001). The expression of genes related to the synthesis and catabolism of endocannabinoids also corroborated the increased plasma 2-arachidonoylglycerol levels in patients with CNP.Conclusions: Endocannabinoid levels, expression of genes related to endocannabinoid metabolism, age, sex, depression and anxiety state together were strong predictors of CNP. The observed molecular changes indicate that lipid metabolism is altered in CNP and thus may represent a viable target for novel analgesics or biomarker development.","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14351"},"PeriodicalIF":4.4000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Clinical Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/eci.14351","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Chronic neuropathic pain (CNP) is a debilitating condition, often refractory to currently available drugs. Understanding biochemical alterations in peripheral tissues such as blood will be useful for understanding underlying pathophysiological processes relating to CNP.

Methods: We collected blood from two independent cohorts of CNP and pain-free controls (CNP n = 129/Controls n = 127) in the UK and Ireland to investigate the relationship between CNP-associated molecular/biochemical alterations and a range of clinical and pain metric parameters. Multiple statistical comparisons were conducted on the data, with selected variables included in one or more of the intended inferential analyses (six models).

Results: Gene expression analysis showed that choline phosphotransferase (CHPT1) was increased (p < .001) in the CNP group compared to controls. The levels of phosphatidylcholine, a metabolite of CHPT1 in the Kennedy Pathway, were significantly (p = .008) decreased in the plasma of patients with CNP. Given the relationship between the Kennedy pathway and endocannabinoids, plasma endocannabinoids and related N-acylethanolamines were quantified in clinical samples by HPLC-Tandem Mass Spectrometry. Plasma levels of the endocannabinoid 2-arachidonoylglycerol were higher in CNP samples compared to controls, and in the statistical models applied, 2-arachidonoylglycerol significantly increased the odds of CNP (p < .001). The expression of genes related to the synthesis and catabolism of endocannabinoids also corroborated the increased plasma 2-arachidonoylglycerol levels in patients with CNP.

Conclusions: Endocannabinoid levels, expression of genes related to endocannabinoid metabolism, age, sex, depression and anxiety state together were strong predictors of CNP. The observed molecular changes indicate that lipid metabolism is altered in CNP and thus may represent a viable target for novel analgesics or biomarker development.

查看原文本刊更多论文

慢性神经病理性疼痛的临床表现与肯尼迪和内源性大麻素途径有关。

背景：慢性神经病理性疼痛（CNP）是一种使人衰弱的病症，目前可用的药物往往难以奏效。了解血液等外周组织的生化变化有助于了解与慢性神经病理性疼痛有关的潜在病理生理过程：我们采集了英国和爱尔兰两组独立的 CNP 和无痛对照组（CNP n = 129/Controls n = 127）的血液，以研究 CNP 相关分子/生化改变与一系列临床和疼痛指标之间的关系。对数据进行了多重统计比较，并将选定变量纳入一个或多个预期推理分析（六个模型）：结果：基因表达分析表明，胆碱磷酸转移酶（CHPT1）增加（p内源性大麻素水平、与内源性大麻素代谢相关的基因表达、年龄、性别、抑郁和焦虑状态共同构成了预测 CNP 的有力因素。观察到的分子变化表明，脂质代谢在中枢神经痛中发生了改变，因此可能成为新型镇痛药或生物标志物开发的可行靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.