Thalamic neuronal and bioenergetic function in painful diabetic peripheral neuropathy: a dual magnetic resonance spectroscopy study

Abstract Aims/hypothesis The aim of this cross-sectional study was to investigate three imaging parameters in people with type 2 diabetes to examine the volume, neuronal function and bioenergetic status of the thalamus in painful diabetic peripheral neuropathy (DPN) compared with painless DPN. Methods Forty-nine participants were recruited: 38 with type 2 diabetes (of whom 11 had painless DPN, nine had diabetes without DPN and 18 had painful DPN) and 11 healthy volunteers. All underwent detailed neurological phenotyping, structural brain MRI, and dual 1 H-MRS and 31 P-MRS during the same study visit. Results Thalamic volume did not differ between groups. However, significant group differences were observed in neuronal function, as assessed by the N -acetylaspartate:choline (NAA:Cho) ratio, and in bioenergetics, as assessed by the inorganic phosphate:ATP (Pi:ATP) ratio. NAA:Cho was significantly higher in individuals with painful DPN than in those with painless DPN. The Pi:ATP ratio was significantly lower in individuals with painful DPN than in those with painless DPN. Moreover, within the painful DPN group, pain intensity correlated with thalamic Pi:ATP, and NAA:Cho significantly correlated with Pi:ATP across the whole cohort. Conclusions/interpretation These findings suggest that an impaired thalamic neuronal and altered bioenergetic state, potentially consistent with impaired oxidative phosphorylation, exists in painless DPN, and that preservation of thalamic bioenergetic and neuronal profiles could be an important central mechanism of painful DPN. These findings may have clinical relevance as metabolites measured by 31 P-MRS may have the potential to act as objective biomarkers of painful DPN or neuropathic pain in future clinical trials.