Aims: Previous neuroimaging studies have demonstrated cerebral structural, functional, and vascular alterations in Painful-Diabetic Peripheral Neuropathy (DPN). We present a multi-modal Magnetic Resonance Imaging (MRI) study to determine the structure, and neuronal and mitochondrial function of the thalamus in Painful-DPN.

Methods: A total of 49 participants were enrolled, 38 with type 2 diabetes (9 without DPN [No-DPN]; 11 with Painless-DPN; and 18 with Painful-DPN) and 11 healthy volunteers (HV). Participants underwent detailed clinical and neurophysiological assessments, and multi-modal MR imaging of the thalami bilaterally including: Proton-Magnetic Spectroscopy (1H-MRS); 31-Phosphorus MRS (31P-MRS); and brain morphometric analysis. We calculated the N-acetyl aspartate to choline (NAA:Cho), a measure of neuronal function, and inorganic phosphate (Pi) to ATP (Pi:ATP), a measure of mitochondrial function.

Results: There were no significant differences in thalamic volume between groups (ANOVA, p=0.927). There was a significant group effect in both metabolite ratios: NAA:Cho (ANOVA, p=0.013); Pi:ATP (p=0.021). The NAA:Cho was numerically the lowest in Painless-DPN, reaching significance compared with HV (p=0.001) and Painful-DPN (p=0.019). Additionally, the Pi:ATP was significantly higher in Painless-DPN compared with HV (p=0.013) and Painful-DPN (p=0.008). There was also a significant correlation between the NAA:Cho and Pi:PCr (Pearson’s r -0.336, p=0.034).

Conclusion: This is the first study to determine perform cerebral 1H- and 31P-MRS in human DPN. We have demonstrated altered 1H- and 31P-MRS ratios in Painless- but not Painful-DPN, suggesting that mitochondrial dysfunction may underlie thalamic neuronal dysfunction in Painless-DPN. Conversely, in Painful-DPN, preservation of thalamic mitochondrial and neuronal function may be involved in the maintenance of neuropathic pain signaling.

Disclosure

G.P.Sloan: None. K.Teh: None. D.Selvarajah: None. S.Tesfaye: Advisory Panel; Bayer Inc., Wörwag Pharma GmbH & Co. KG, Angelini, Speaker's Bureau; Viatris Inc., Nevro Corp., Procter & Gamble, Novo Nordisk, Berlin-Chemie AG.

© 2023 by the American Diabetes Association
2023
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