Aims: Altered functional connectivity has been identified in key brain regions involved in somatosensory perception in patients with painful diabetic peripheral neuropathy (painful-DPN) , using resting state functional-magnetic resonance imaging (fMRI) . This study aimed to examine the impact of neuropathic pain treatments on these regions.

Methods: Fifteen participants with Painful-DPN enrolled in the OPTION-DM clinical trial underwent underwent fMRI imaging using 3T when the participants were on maximum tolerated medication (Treatment Scan) and one week after medication washout (Washout Scan) . The data was analysed using Conn Functional Connectivity Toolbox in SPM.

Results: There was a significant increase in Pain Numeric Rating Scale (NRS) from Treatment Scan (4.0 ± 2.1) to the Washout Scan (6.1 ± 2.4, p=0.044) with a corresponding rise in functional connectivity between the Primary Somatosensory Cortex (S1) and the Thalamus, and the Insular Cortex and Thalamus (p=0.041) . There was a significant difference in the change between scans in S1 - Thalamic functional connectivity in participants with Severe-Pain (NRS ≥8 at baseline: -0.372 ± 0.275) compared to participants with Moderate-Pain (NRS ≤7: -0.051 ± 0.180, p=0.035) . The change in S1-Thalamic connectivity also correlated with baseline pain (r -0.585, p=0.022) and the difference in NRS at the Treatment Scan and Baseline pain (r -0.513, p=0.050) .

Conclusions: On neuropathic pain medication withdrawal there is an increase S1 - Thalamus and Insular Cortex - Thalamus functional connectivity. Moreover, the change in S1 - Thalamus functional connectivity from the Treatment Scan to Withdrawal Scan differentiated participants with high and low baseline neuropathic pain. This study demonstrates that thalamic functional connectivity to the S1 and Insular Cortex has the potential to act as a biomarker of painful-DPN.


G.P.Sloan: None. D.Selvarajah: None. K.Teh: None. S.Tesfaye: Advisory Panel; Astellas Pharma Inc., Bayer AG, Grünenthal Group, Nevro Corp., Wörwag Pharma GmbH & Co. KG, Speaker's Bureau; Eva Pharma, Pfizer Inc., Viatris Inc.

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