Abstract

Objective: We have previously reported increased thalamic vascularity in painful diabetic peripheral neuropathy (PDPN) but the microvascular perfusion characteristics of the other pain processing areas of the brain (Pain Matrix - PM) with or without pain at the time of scanning have not been assessed. The aim thus was to measure the cerebral perfusion of the PM areas using MR-Dynamic Susceptibility Contrast (MR-DSC). Methods: 55 T1DM subjects (20 PDPN, 23 painless-DPN, 13 no-DPN) and 19 healthy volunteers (HV) underwent clinical, neurophysiological and MR-DSC of the passage of IV-gadolinium-chelate through the cerebral vascular bed (3-Tesla, Philips, Netherlands) at rest. The PDPN group was further divided into those that had neuropathic pain during scan - P+ and no pain - P-) and the intensity of pain at the time of scanning was recorded. The Mean Transit Time -MTT and the time-to-peak -TTP concentrations of gadolinium in PM areas (Thalamus, Insular Cortex - IC, Anterior Cingulate Cortex - ACC) were measured. Results: Subjects experiencing spontaneous neuropathic pain (P+, n=10, VAS score≥4) during scanning had shorter mean TTP at the Right-Thalamus: P+ vs. painless-DPN p=0.017, P+ vs. HV p=0.033; Right-IC: P+ vs. painless-DPN p=0.048; and POWM: P+ vs. P- p=0.009, P+ vs. painless-DPN p=0.034, P+ vs. HV p=0.011. The MTT at the Right-Thalamus: P+ vs. HV p=0.043 and at the Left-IC: HV vs. No-DPN p=036, were also significant. Conclusion: This is the first study to show there is altered cerebral perfusion in the pain processing areas of of the brain, with shorter TTP during spontaneous pain at the time of scanning. This seems to be related to a bolus dispersal factor as MTT, and CBF do not match the TTP and the control area is also affected. However, whether this altered perfusion is primary or secondary to the experience of pain is yet to be determined. This novel finding may serve as objective marker of spontaneous neuropathic pain, and a target for the development of novel treatments. Disclosure M. Greig: None. G. P. Sloan: None. P. Shillo: None. D. Selvarajah: None. I. D. Wilkinson: 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. Funding European Foundation for the Study of Diabetes

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