Determinants of Treatment Response in Painful Diabetic Peripheral Neuropathy. A Combined Deep Sensory Phenotyping and Multi-modal Brain Magnetic Resonance Imaging Study.

Painful diabetic polyneuropathy (DPN) is difficult to manage as treatment response is often varied. The primary aim of this study was to examine differences in pain phenotypes between responders and non-responders to intravenous lidocaine treatment using quantitative sensory testing. The secondary aim was to explore differences in brain structure and functional connectivity with treatment response. Forty-five consecutive patients who received intravenous lidocaine treatment for painful DPN were screened. Twenty-nine patients who met the eligibility criteria (responders n=14 and non-responders n=15) and 26 healthy controls underwent detailed sensory profiling. Subjects also underwent multimodal brain magnetic resonance (MR) imaging. Greater proportion of patients with the irritable (IR) nociceptor phenotype were responders to intravenous lidocaine treatment compared to non-responders . The odd-ratio of responding to intravenous lidocaine was 8.67 times greater (95%CI 1.4:53.8) for the IR nociceptor phenotype. Responders to intravenous lidocaine also had significantly greater mean S1 cortical volume and functional connectivity between the insula cortex and the corticolimbic circuitry. This study provides preliminary evidence for a mechanism-based approach for individualising therapy in patients with painful DPN.