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 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 characterised cohort of participants with Painless- and Painful-DPN. Participants with DPN (Painful- and Painless combined) had a significantly lower GABA:H2O ratio compared to those without DPN (Healthy volunteers [HV] and 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.

This article contains supplementary material online at https://doi.org/10.2337/figshare.25864495.

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