Background: Painful diabetic polyneuropathy (DPN) is difficult to manage as treatment response is often varied. The aim of this study was to explore the central mechanisms to explain the variance in treatment response.
Methods: Forty-five consecutive patients who received intravenous lidocaine treatment for painful DPN were screened. All subjects completed a treatment efficacy questionnaire. Twenty-nine patients (responders n=14 and non-responders n=15) along with 26 healthy controls subsequently underwent multimodal brain magnetic resonance (MR) imaging to acquire anatomical and resting state functional data (3T, Achieva, Phillips Healthcare).
Results: There was no significant difference in age (p=0.53), pain duration (p=0.89), diabetes duration (p=0.19) and clinical parameters of neuropathy (TCNS, p=0.16 and NTSS-6, p=0.61) between responders and non-responders to lidocaine treatment. Neither was there a difference in the use of concurrent neuropathic pain treatments. Non-responders to lidocaine had significantly lower mean S1 cortical volumes and mean number of vertices compared to responders and healthy controls (ANOVA p=0.02 and 0.02 respectively). There was no significant difference in S1 cortical volumes or vertices between responders and healthy controls. There was significantly greater resting state functional connectivity in lidocaine responders between the insula cortex [F(4)(13)=10.33; p-FDR=0.01] and the orbital frontal cortex [T(20)=3.88; p-FDR=0.02], amygdala [T(20)=3.65; p-FDR=0.02] and anterior cingulate gyrus [T(20)=4.04; p-FDR=0.01].
Conclusion: To the best of our knowledge, this is the first assessment of CNS mechanisms of treatment response in painful DPN. Key nociceptive processing areas showed decreased grey matter density (S1 cortex) and reduced functional connectivity (insula) relating to treatment response. MR neuroimaging may serve as a Central Pain Signature which could be used to predict treatment response.
K. Teh: None. I.D. Wilkinson: None. G.P. Sloan: None. S. Tesfaye: Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation, Wörwag Pharma. Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, Napp Pharmaceuticals, Novo Nordisk Inc., Pfizer Inc. D. Selvarajah: None.
European Foundation for the Study of Diabetes; University of Sheffield