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

  • Microvascular Complications—Neuropathy (R Pop-Busui, Section Editor)
  • Published:
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Abstract

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.

Summary

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.

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Acknowledgments

This study is supported by National Institutes for Health awards DK057629 (NAC), DP3DK108245 (NAC), and DK081082 (NAC and RAM) and American Diabetes Association Award 1-17-ICTS-062 (AGM, NAC).

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Authors and Affiliations

  1. The Salk Institute for Biological Sciences, La Jolla, CA, USA

    Corinne Lee-Kubli

  2. Faculty of Medical and Human Sciences, Institute of Cardiovascular Sciences, University of Manchester and National Institute for Healthy Research/Wellcome Trust Clinical Research Facility, Manchester, UK

    Andrew G. Marshall & Rayaz A. Malik

  3. Department of Clinical Neurophysiology, Salford Royal Hospital, National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK

    Andrew G. Marshall

  4. Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar

    Rayaz A. Malik

  5. Department of Pathology, University of California San Diego, La Jolla, CA, USA

    Nigel A. Calcutt

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  1. Corinne Lee-Kubli
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  4. Nigel A. Calcutt
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Correspondence to Nigel A. Calcutt.

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Corinne Lee-Kubli, Andrew G. Marshall, Rayaz A. Malik, and Nigel A. Calcutt declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

Previously unpublished data (Fig. 1) was collected by Corinne Lee-Kubli and Nigel Calcutt using the UCSD IACUC-approved protocol S-02059R.

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This article is part of the Topical Collection on Microvascular Complications—Neuropathy

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Lee-Kubli, C., Marshall, A.G., Malik, R.A. et al. The H-Reflex as a Biomarker for Spinal Disinhibition in Painful Diabetic Neuropathy. Curr Diab Rep 18, 1 (2018). https://doi.org/10.1007/s11892-018-0969-5

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