Diabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, U.K.
Division of Clinical Medicine, University of Sheffield, Sheffield, U.K.
Diabetes. 2024 Aug 1;73(8):1317-1324. doi: 10.2337/db23-0921.
Alterations in the structure, function, and microcirculation of the thalamus, a key brain region involved in pain pathways, have previously been demonstrated in patients with painless and painful diabetic peripheral neuropathy (DPN). However, thalamic neurotransmitter levels including γ-aminobutyric acid (GABA) (inhibitory neurotransmitter) and glutamate (excitatory neurotransmitter) in different DPN phenotypes are not known. We performed a magnetic resonance spectroscopy study and quantified GABA and glutamate levels within the thalamus, in a carefully characterized cohort of participants with painless and painful DPN. Participants with DPN (painful and painless combined) had a significantly lower GABA:H2O ratio compared with those without DPN (healthy volunteers [HV] and participants with diabetes without DPN [no DPN]). Participants with painless DPN had the lowest GABA:H2O ratio, which reached significance compared with HV and no DPN, but not painful DPN. There was no difference in GABA:H2O in painful DPN compared with all other groups. A significant correlation with GABA:H2O and neuropathy severity was also seen. This study demonstrates that lower levels of thalamic GABA in participants with painless DPN may reflect neuroplasticity due to reduced afferent pain impulses, whereas partially preserved levels of GABA in painful DPN may indicate that central GABAergic pathways are involved in the mechanisms of neuropathic pain in diabetes.
先前的研究已经表明，在无痛和有痛糖尿病周围神经病变（DPN）患者中，参与疼痛通路的关键大脑区域——丘脑的结构、功能和微循环发生了改变。然而，不同 DPN 表型的丘脑神经递质水平，包括γ-氨基丁酸（GABA）（抑制性神经递质）和谷氨酸（兴奋性神经递质），尚不清楚。我们在一个精心挑选的无痛和有痛 DPN 参与者队列中进行了磁共振波谱研究，并定量了丘脑内的 GABA 和谷氨酸水平。与无 DPN 者（健康志愿者[HV]和无 DPN 的糖尿病患者[无 DPN]）相比，有 DPN（疼痛和无痛合并）者的丘脑 GABA:H2O 比值显著降低。无痛 DPN 参与者的 GABA:H2O 比值最低，与 HV 和无 DPN 相比均有显著差异，但与有痛 DPN 相比无差异。有痛 DPN 者的 GABA:H2O 比值与其他各组无差异。还观察到 GABA:H2O 与神经病变严重程度的显著相关性。本研究表明，无痛 DPN 参与者丘脑内 GABA 水平较低可能反映了传入性疼痛冲动减少导致的神经可塑性，而有痛 DPN 中 GABA 水平部分保留可能表明中枢 GABA 能通路参与了糖尿病性神经病理性疼痛的机制。
