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Dinesh Italian Diabetes Society.pptx
- 1. I am currently Senior Lecturer in Diabetes at University of Sheffield. My research focus is applying multimodal magnetic resonance neuroimaging to characterize the central pain mechanisms in diabetic neuropathy. I am amongst the world’s leading clinical researches looking into the causes, treatment and prevention of diabetic neurpathy, exemplified by my award of 1st Prize at the 5th NeupSIG International Congress on Neuropathic Pain (2015), the Goran Sundquist NeuroDIAB Prize for Young Clinical Investigator of the Year (2012), 1st prize at Finnish Diabetes Association ‘Diabetes a Threat to Mankind’ Research (2013) and the STEM for Britain Research Award for Biomedical Science by the Parliamentary and Scientific Committee (2011). Dr Dinesh Selvarajah MBChB, MRCP, PhD
- 2. Diabetic Neuropathy: New Insights from Brain Imaging Dr Dinesh Selvarajah Senior Lecturer in Diabetes Department of Human Metabolism University of Sheffield Sheffield, UK
- 3. Symmetric, length dependent, sensory-motor neuropathy Affects 30-50% of all diabetic people1 Strongest risk factor for foot ulcer1 and amputation2 Diabetic Polyneuropathy (DPN) Pain
- 4. “I experience sharp electric shocks that shoot up my legs” “When I walk it feels as if I am stepping on broken glass” Pain in diabetic neuropathy
- 5. Multidimensionality of Painful DPN Anxiety Depression Anger Fear Loss of confidence Psychological Job loss Marital disharmony Isolation Loss of social status Social
- 6. Topical lidocaine Topiramate* Antidepressants, SSRI Capsaicin NMDA antagonists* Mexiletine* Antidepressants, SNRI Gabapentin/Pregabalin Tramadol Opioids Carbamazepine/lamotrigine/Pheny Valproate Tricyclic antidepressants 0 2 4 6 8 10 12 397 109 83 389 120 778 1057 149 81 466 150 214 NA NNT Jensen TS, et al. Diab Vasc Dis Res. 2006 NNT > 50% Pain Reduction >50% relief in ~1/3
- 9. Non Irritable Nociceptor Phenotype Irritable nociceptor Phenotype Painful DPN Clinical Phenotypes n=147
- 12. Pathogenesis of DN Diabetic insult may be more generalised Peripheral lesions Central lesions +
- 13. Diffusion Tensor Imaging/ Tractography Volumetric measures Multi-modal Advanced MRI paradigm shift Resting fMRI Task fMRI/ Perfusion Imaging Multi-modal Advanced MRI paradigm shift H+Spectoscopy
- 17. Areas of significant change in the endogenous opioid transmission during pain-related experiences Areas of greater functional connectivity in responders to neuropathic pain treatment HYPOTHESIS: Responders to neuropathic pain treatment have better target engagement of opioid receptor systems compared to non-responders
- 18. MOOD Depression Anxiety Pain Catastrophizing CONTEXT Pain Beliefs Expectations Placebo COGNITION Hyper- vigilance Distraction Attention NEUROCHEMICAL & STRUCTURAL CHANGES Disease e.g. DN Maladaptive plasticity Neurodegeneration NOCICEPTIVE INPUT Pain modulation
- 19. ICA Deep Learning Classification Workflow A - 30 group-level ICA networks from all subjects B - 7 and 30 components chosen C - Dual regression to extract subject specific spatial ICA maps D - 5-fold cross validation (18/5- train/test split) E - Train tuning and testing D
- 21. • Significant CNS involvement in DPN • Pain phenotyping will be increasingly utilised in RCTs to stratify those that may respond to a particular treatment. • Neuroimaging may have a role in pain phenotyping • Advances in artificial intelligence and machine learning will facillitate this Conclusions
- 22. Thank You