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Brain GABA and glutamate levels across pain conditions: A systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool
NeuroImage ( IF 5.7 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.neuroimage.2020.116532
Aimie Laura Peek 1 , Trudy Rebbeck 1 , Nicolaas Aj Puts 2 , Julia Watson 3 , Maria-Eliza R Aguila 4 , Andrew M Leaver 1
Affiliation  

BACKGROUND A proposed mechanism of chronic pain is dysregulation between the main inhibitory (GABA) and excitatory (glutamate) neurometabolites of the central nervous system. The level of these neurometabolites appears to differ in individual studies of people with pain compared to pain-free controls across different pain conditions. However, this has yet to be systematically investigated. AIMS To establish whether GABA, glutamate, glutamine and Glx levels differ across pain conditions when compared to pain-free controls. METHODS Five databases were searched. Studies were included if they investigated: 1) A pain condition compared to control. 2) Reported GABA, glutamate, glutamine or glutamate/glutamine level. 3) Used 1H-Magnetic Resonance Spectroscopy (Prospero Project ID CRD42018092170). Data extracted included neurometabolite level, pain diagnosis, and spectroscopy parameters. Meta-analyses were conducted to establish the difference in neurometabolite level between participants with pain and pain-free controls for different pain conditions. The MRS-Q was developed from existing clinical consensus to allow for the assessment of quality in the included studies. RESULTS Thirty-five studies were included investigating combinations of migraine (n = 11), musculoskeletal pain (n = 8), chronic pain syndromes (n = 9) and miscellaneous pain (n = 10). Higher GABA levels were found in participants with migraine compared to controls (Hedge's G 0.499, 95%CI: 0.2 to 0.798). In contrast, GABA levels in musculoskeletal pain conditions (Hedge's G -0.189, 95%CI: 0.530 to 0.153) and chronic pain syndromes (Hedge's G 0.077, 95%CI: 1.612 to 1.459) did not differ from controls. Results for other brain neurometabolites revealed significantly higher levels for glutamate in participants with migraine and Glx in chronic pain syndromes compared to controls. CONCLUSION These results support the theory that underlying neurometabolite levels may be unique in different pain conditions and therefore representative of biomarkers for specific pain conditions.

中文翻译:

不同疼痛状况下的脑 GABA 和谷氨酸水平:使用 MRS-Q 质量评估工具对 1H-MRS 研究进行系统文献回顾和荟萃分析

背景 慢性疼痛的提出机制是中枢神经系统的主要抑制性(GABA)和兴奋性(谷氨酸)神经代谢物之间的失调。与不同疼痛条件下的无痛对照相比,这些神经代谢物的水平在对疼痛患者的个别研究中似乎有所不同。然而,这还有待系统地研究。目的 确定与无痛对照组相比,GABA、谷氨酸、谷氨酰胺和 Glx 水平是否因疼痛状况而异。方法检索了五个数据库。如果他们调查:1) 与对照相比的疼痛状况,则研究被包括在内。2) 报告的 GABA、谷氨酸、谷氨酰胺或谷氨酸/谷氨酰胺水平。3) 使用 1H-磁共振光谱(Prospero 项目 ID CRD42018092170)。提取的数据包括神经代谢物水平,疼痛诊断和光谱参数。进行了荟萃分析,以确定不同疼痛状况的疼痛参与者和无痛对照组之间神经代谢物水平的差异。MRS-Q 是根据现有的临床共识制定的,以便评估纳入研究的质量。结果 纳入了 35 项研究,调查偏头痛 (n = 11)、肌肉骨骼疼痛 (n = 8)、慢性疼痛综合征 (n = 9) 和其他疼痛 (n = 10) 的组合。与对照组相比,偏头痛参与者的 GABA 水平更高(Hedge's G 0.499,95% CI:0.2 至 0.798)。相比之下,肌肉骨骼疼痛病症 (Hedge's G -0.189, 95% CI: 0.530 to 0.153) 和慢性疼痛综合征 (Hedge's G 0.077, 95%CI: 1.612 to 1.459) 中的 GABA 水平与对照组没有差异。其他脑神经代谢物的结果显示,与对照组相比,患有偏头痛和慢性疼痛综合征的 Glx 参与者的谷氨酸水平显着更高。结论 这些结果支持以下理论,即潜在的神经代谢物水平在不同的疼痛状况中可能是独一无二的,因此代表了特定疼痛状况的生物标志物。
更新日期:2020-04-01
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