循环多不饱和脂肪酸、压痛阈值与神经源性疼痛状况
Circulating polyunsaturated fatty acids, pressure pain thresholds, and nociplastic pain conditions.
作者信息
Sanders Anne E, Weatherspoon E Diane, Ehrmann Brandie M, Soma Paul S, Shaikh Saame R, Preisser John S, Ohrbach Richard, Fillingim Roger B, Slade Gary D
机构信息
Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States of America.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
出版信息
Prostaglandins Leukot Essent Fatty Acids. 2022 Sep;184:102476. doi: 10.1016/j.plefa.2022.102476. Epub 2022 Jul 23.
OBJECTIVE
Polyunsaturated fatty acids (PUFAs) play a role in pain regulation. This study sought to determine whether free PUFAs found in red blood cells also play a role in nociceptive processing. We examined associations between circulating PUFAs and nociceptive thresholds to noxious mechanical stimuli. We also determined whether nociceptive thresholds were associated with nociplastic pain conditions.
METHODS
This cross-sectional study used stored red bloods cells and data from 605 adult participants in the OPPERA-2 study of chronic overlapping pain conditions. In OPPERA-2 adults completed quantitative sensory testing in which pressure algometry measured deep muscular tissue sensitivity at six anatomical sites. Standardized protocols classified adults for presence or absence of five nociplastic pain conditions: temporomandibular disorder, headache, low back pain, irritable bowel syndrome and fibromyalgia. Liquid chromatography tandem mass spectroscopy quantified erythrocyte PUFAs. We conducted three sets of analyses. First, a multivariable linear regression model assessed the association between n-6/n-3 PUFA ratio and the number of overlapping nociplastic pain conditions. Second, a series of 36 multivariable linear regression models assessed covariate-adjusted associations between PUFAs and nociceptive thresholds at each of six anatomical sites. Third, a series of 30 multivariable linear regression models assessed covariate-adjusted associations between nociceptive thresholds at six anatomical sites and each of five pain conditions.
RESULTS
In multiple linear regression, each unit increase in n-6/n-3 PUFA ratio was associated with more pain conditions (β = 0.30, 95% confidence limits: 0.07, 0.53, p = 0.012). Omega-6 linoleic acid and arachidonic acid were negatively associated with lower nociceptive thresholds at three and at five, respectively, anatomical sites. In contrast, omega-3 alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and the n-6/n-3 PUFA ratio were not associated with nociceptive thresholds at any site. Pain cases had significantly lower nociceptive thresholds than non-case controls at all anatomical sites.
CONCLUSION
A higher n-6/n-3 PUFA ratio was associated with more pain conditions. Omega-6 PUFAs may promote a generalized upregulation of nociceptive processing.
目的
多不饱和脂肪酸（PUFAs）在疼痛调节中发挥作用。本研究旨在确定红细胞中游离的PUFAs是否也在伤害性加工中起作用。我们研究了循环PUFAs与对有害机械刺激的伤害性阈值之间的关联。我们还确定了伤害性阈值是否与神经病理性疼痛状况相关。
方法
这项横断面研究使用了储存的红细胞以及来自OPPERA - 2慢性重叠疼痛状况研究中605名成年参与者的数据。在OPPERA - 2研究中，成年人完成了定量感觉测试，其中压力测痛法测量了六个解剖部位的深部肌肉组织敏感性。标准化方案根据是否存在五种神经病理性疼痛状况对成年人进行分类：颞下颌关节紊乱、头痛、腰痛、肠易激综合征和纤维肌痛。液相色谱串联质谱法定量红细胞PUFAs。我们进行了三组分析。首先，一个多变量线性回归模型评估了n - 6/n - 3 PUFA比值与重叠神经病理性疼痛状况数量之间的关联。其次，一系列36个多变量线性回归模型评估了PUFAs与六个解剖部位中每个部位的伤害性阈值之间经协变量调整后的关联。第三，一系列30个多变量线性回归模型评估了六个解剖部位的伤害性阈值与五种疼痛状况中每种状况之间经协变量调整后的关联。
结果
在多元线性回归中，n - 6/n - 3 PUFA比值每增加一个单位，与更多的疼痛状况相关（β = 0.30，95%置信区间：0.07，0.53，p = 0.012）。ω - 6亚油酸和花生四烯酸分别与三个和五个解剖部位较低的伤害性阈值呈负相关。相比之下，ω - 3α - 亚麻酸、二十碳五烯酸、二十二碳六烯酸以及n - 6/n - 3 PUFA比值与任何部位的伤害性阈值均无关联。在所有解剖部位，疼痛患者的伤害性阈值显著低于非疼痛对照。
结论
较高的n - 6/n - 3 PUFA比值与更多的疼痛状况相关。ω - 6 PUFAs可能促进伤害性加工的普遍上调。
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