Peripheral and Central Biomarkers of Painful Diabetic Neuropathy

• Research type

  Research Study

• Full title

  Peripheral and Central Biomarkers of Painful Diabetic Peripheral Neuropathy

• IRAS ID

  227603

• Contact name

  Solomon Tesfaye

• Contact email

  solomon.tesfaye@sth.nhs.uk

• Sponsor organisation

  Sheffield Teaching Hospitals

• Duration of Study in the UK

  2 years, 0 months, 1 days

• Research summary

  Up to a third of people with diabetes can develop nerve damage, neuropathy, in their feet and legs. This can lead to a loss of sensation and in some, severe pain. Previous studies have found differences on skin biopsy and brain scanning in neuropathy but the underlying cause, particularly of painful symptoms, remains unknown.
  The study will look into the differences found in the brain, spinal cord and skin nerves in people with diabetic neuropathy. We will compare different groups of people including: healthy volunteers, patients with type 2 diabetes without neuropathy, with established painful neuropathy, established painless neuropathy, and, as a pilot, early painful neuropathy (less than 2 years since diagnosis). Patients will undergo clinical assessment, neurophysiological assessment, skin biopsy and magnetic resonance imaging.
  The study will investigate how several potential peripheral skin biopsy biomarkers of painful diabetic neuropathy interact with clinical phenotypes and central manifestations of painful diabetic neuropathy. The long-term objective is to identify biomarkers of painful neuropathy that can be used: (i) to detect early neuropathic involvement suitable for therapeutic intervention and (ii) as markers with which to monitor treatment response and outcome.

  Summary of Results
  Study 1
  People with painful diabetic nerve damage showed more activity and energy use in the brain’s pain-processing area than people with nerve damage but no pain. The worse the pain, the harder this part of the brain was working. This suggests painful DPN involves overactive pain signals in the brain, not just damaged nerves in the feet.
  Study 2:
  Both painful and painless diabetic nerve damage involved loss of small nerve fibers in the skin, but people with pain also had many more blood vessels around the remaining nerves. This imbalance was strongest in the feet and lower legs and was linked to worse pain. It suggests pain may be caused by over-stimulation of the remaining nerves, which helps explain why symptoms start in the feet

  Study 3:
  Brain scans showed that people with diabetic nerve damage have physical changes in the brain areas that control feeling and pain. These changes were greater when nerve damage was more severe, and different in people with pain compared with those without pain. This shows diabetic nerve pain is linked to real, measurable changes in the brain, not just nerve damage in the limbs
  

• REC name

  East Midlands - Nottingham 1 Research Ethics Committee

• REC reference

  17/EM/0430

• Date of REC Opinion

  18 Dec 2017

• REC opinion

  Further Information Favourable Opinion