Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways
Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways
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DOI：
10.1016/s0304-3959(00)00284-0
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发表时间：
2000-08-01
期刊：
影响因子：
7.4
通讯作者：
Michalek, JE
中科院分区：
文献类型：
--
作者：
Larson, AA;Giovengo, SL;Michalek, JE
纤维肌痛综合征（FMS）患者脑脊液中的P物质（SP），一种假定的伤害性递质，增加。由于兴奋性氨基酸（EAA）也似乎传递疼痛，我们假设，CSF EAA可能类似地参与这种综合征。我们发现，CSF中大多数氨基酸的平均浓度在原发性FMS（PFMS）、与其他疾病相关的纤维肌痛（SFMS）、未表现出纤维肌痛的其他疼痛性疾病（OTHER）或年龄匹配的健康正常对照（HNC）受试者组之间没有差异。然而，在SFMS患者中，使用基于检查的疼痛强度测量（压痛点指数（TPI））确定的疼痛强度个体测量值分别与谷氨酰胺和天冬酰胺（谷氨酸和天冬氨酸的代谢物）的浓度相关。这表明再摄取和生物转化掩盖了疼痛相关的EAA增加。在PFMS患者中，甘氨酸和牛磺酸的个体浓度也与其各自的TPI值相关。虽然牛磺酸受到各种兴奋性操作的影响，但甘氨酸是抑制性递质，也是N-甲基-D-谷氨酸（NMDA）受体的正调节剂。在PFMS和SFMS患者中，TPI与精氨酸（一氧化氮（NO）的前体）共变，精氨酸的浓度反过来与瓜氨酸（NO合成的副产物）的浓度相关。这些事件预示着NO的参与，NO是一种被认为参与疼痛处理的有效信号分子。这些代谢变化与FMS患者的疼痛强度相关，可能反映了EAA释放增加和甘氨酸对NMDA受体的正调节，可能导致NO合成增强。（C）2000国际疼痛研究协会。由Elsevier Science B. V.出版，版权所有。
Substance P (SP), a putative nociceptive transmitter, is increased in the CSF of patients with fibromyalgia syndrome (FMS). Because excitatory amino acids (EAAs) also appear to transmit pain, we hypothesized that CSF EAAs may be similarly involved in this syndrome. We found that the mean concentrations of most amino acids in the CSF did not differ amongst groups of subjects with primary FMS (PFMS), fibromyalgia associated with other conditions (SFMS), other painful conditions not exhibiting fibromyalgia (OTHER) or age-matched, healthy normal controls (HNC). However, in SFMS patients, individual measures of pain intensity, determined using an examination-based measure of pain intensity, the tender point index (TPI), covaried with their respective concentrations of glutamine and asparagine, metabolites of glutamate and aspartate, respectively. This suggests that re-uptake and biotransformation mask pain-related increases in EAAs. Individual concentrations of glycine and taurine also correlated with their respective TPI values in patients with PFMS. While taurine is affected by a variety of excitatory manipulations, glycine is an inhibitory transmitter as well as a positive modulator of the N-methyl-D-asparate (NMDA) receptor. In both PFMS and SFMS patients, TPI covaried with arginine, the precursor to nitric oxide (NO), whose concentrations, in turn, correlated with those of citrulline, a byproduct of NO synthesis. These events predict involvement of NO, a potent signaling molecule thought to be involved in pain processing. Together these metabolic changes that covary with the intensity of pain in patients with FMS may reflect increased EAA release and a positive modulation of NMDA receptors by glycine, perhaps resulting in enhanced synthesis of NO. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.