Reduced Thalamic γ-Aminobutyric Acid (GABA) in Painless but Not Painful Diabetic Peripheral Neuropathy.

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 GABAH2O ratio compared with those without DPN (healthy volunteers [HV] and participants with diabetes without DPN [no DPN]). Participants with painless DPN had the lowest GABAH2O ratio, which reached significance compared with HV and no DPN, but not painful DPN. There was no difference in GABAH2O in painful DPN compared with all other groups. A significant correlation with GABAH2O 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.