1. Reduced Thalamic γ-Aminobutyric Acid (GABA) in Painless but Not Painful Diabetic Peripheral Neuropathy.
- Author
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Shillo, Pallai, Sloan, Gordon, Selvarajah, Dinesh, Greig, Marni, Gandhi, Rajiv, Anand, Praveen, Edden, Richard A., Wilkinson, Iain D., and Tesfaye, Solomon
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DIABETIC neuropathies ,GABA ,NUCLEAR magnetic resonance spectroscopy ,NEURALGIA ,GLUTAMIC acid - Abstract
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:H
2 O 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:H2 O ratio, which reached significance compared with HV and no DPN, but not painful DPN. There was no difference in GABA:H2 O in painful DPN compared with all other groups. A significant correlation with GABA:H2 O 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. Article Highlights: The thalamus has been shown to play a key role in the cerebral mechanisms of diabetic peripheral neuropathy (DPN), but neurotransmitter levels have not been explored. We sought to determine the levels of excitatory (glutamate) and inhibitory (γ-aminobutyric acid [GABA]) neurotransmitter levels in the thalamus in participants with painful and painless DPN. Thalamic GABA levels were reduced in participants with painless DPN, with partially preserved levels seen in painful DPN. Alterations of thalamic GABAergic pathways could be involved in the central mechanisms of both painful and painless DPN. [ABSTRACT FROM AUTHOR]- Published
- 2024
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