Thalamic neuronal and bioenergetic function in painful diabetic peripheral neuropathy: a dual magnetic resonance spectroscopy study
- 1Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- 2Division of Clinical Medicine, University of Sheffield, Sheffield, UK
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 1H-MRS and 31P-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 31P-MRS may have the potential to act as objective biomarkers of painful DPN or neuropathic pain in future clinical trials.
Graphical Abstract:
Supplementary Information: The online version contains peer-reviewed but unedited supplementary material available at https://doi.org/10.1007/s00125-026-06846-8.
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BibTeX
@article{sloan2026thalamic,
title = {{Thalamic neuronal and bioenergetic function in painful diabetic peripheral neuropathy: a dual magnetic resonance spectroscopy study}},
author = {Gordon Sloan and Adriana Anton and Kevin Teh and Sharon Caunt and Ancy Thomas and Iain Wilkinson and Dinesh Selvarajah and Solomon Tesfaye},
journal = {Diabetologia},
year = {2026},
month = sep,
doi = {10.1007/s00125-026-06846-8},
url = {https://doi.org/10.1007/s00125-026-06846-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Thalamic neuronal and bioenergetic function in painful diabetic peripheral neuropathy: a dual magnetic resonance spectroscopy study
AU - Gordon Sloan
AU - Adriana Anton
AU - Kevin Teh
AU - Sharon Caunt
AU - Ancy Thomas
AU - Iain Wilkinson
AU - Dinesh Selvarajah
AU - Solomon Tesfaye
PY - 2026
DA - 2026/09/10
JO - Diabetologia
DO - 10.1007/s00125-026-06846-8
UR - https://doi.org/10.1007/s00125-026-06846-8
AB - 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 1H-MRS and 31P-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 31P-MRS may have the potential to act as objective biomarkers of painful DPN or neuropathic pain in future clinical trials. Graphical Abstract: Supplementary Information: The online version contains peer-reviewed but unedited supplementary material available at https://doi.org/10.1007/s00125-026-06846-8.
SN - 0012-186X
SN - 1432-0428
ER -