Abstract

Painful diabetic neuropathy (DN) is a common, distressing complication of diabetes that is discordant with the degree of peripheral nerve pathology. Very little is known about the cerebral processes involved in pain processing in painful DN. Here we investigated resting-state brain connectivity associated with prolonged pain in DN. Methods: 58 subjects and 36 matched controls were compared with regard to both behavioural measures of pain perception and resting-resting state functional Magnetic Resonance Imaging. The resting-state fMRI brain connectivity was investigated using 20 seed regions located in cardinal pain processing brain regions. Resting-state fMRI analysis was performed using the NITRC Functional Connectivity (CONN) Toolbox and SPM8 (welcome Trust Centre for Neuroimaging London, UK) in Matlab 2014a (the MathWorks, Natick, MA, USA). Functional connectivity matrices between the pre-specified seeds were calculated and the HV versus painful DN phenotype interaction examined. Results: Relative to controls, painful DPN patients displayed increased brain connectivity predominately for the supplementary motor areas (p<0.01) and the primary sensorimotor cortex (p<0.001). Similar results were found when painful DPN subjects were compared with those with No DPN. Conversely, we observed an increase in brain connectivity between the primary somatosensory cortex and cingulate cortex (p<0.01), prefrontal cortex (p<0.01) and amygdala (p<0.01) between painful and painless DPN patients. Conclusion: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in painful DPN patients. Disclosure K. Teh: None. I. D. Wilkinson: None. P. Shillo: None. G. P. Sloan: None. S. Tesfaye: Advisory Panel; Self; Angellini, Bayer AG, Eva Pharma, Wörwag Pharma, Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, MSD Corporation, Novo Nordisk, Pfizer Inc. D. Selvarajah: None. Funding Health Education England/University of Sheffield Knowledge Exchange Fund; National Institute for Health Research; EME

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