The H-Reflex as a Biomarker for Spinal Disinhibition in Painful Diabetic Neuropathy

Curr Diab Rep. 2018 Jan 23;18(1):1. doi: 10.1007/s11892-018-0969-5.


Purpose of review: Neuropathic pain may arise from multiple mechanisms and locations. Efficacy of current treatments for painful diabetic neuropathy is limited to an unpredictable subset of patients, possibly reflecting diversity of pain generator mechanisms, and there is a lack of targeted treatments for individual patients. This review summarizes preclinical evidence supporting a role for spinal disinhibition in painful diabetic neuropathy, the physiology and pharmacology of rate-dependent depression (RDD) of the spinal H-reflex and the translational potential of using RDD as a biomarker of spinally mediated pain.

Recent findings: Impaired RDD occurs in animal models of diabetes and was also detected in diabetic patients with painful vs painless neuropathy. RDD status can be determined using standard neurophysiological equipment. Loss of RDD may provide a clinical biomarker of spinal disinhibition, thereby enabling a personalized medicine approach to selection of current treatment options and enrichment of future clinical trial populations.

Keywords: Diabetic neuropathy; H-reflex; KCC2; Neuropathic pain; Rate-dependent depression; Spinal disinhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Depression
  • Diabetic Neuropathies / physiopathology*
  • H-Reflex / physiology*
  • Humans
  • Neural Inhibition / physiology*
  • Neuralgia / physiopathology*
  • Spinal Nerves / physiology
  • Spinal Nerves / physiopathology
  • gamma-Aminobutyric Acid / physiology


  • Biomarkers
  • gamma-Aminobutyric Acid