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Painful Diabetic Polyneuropathy pp 13–26Cite as

Biology and Pathophysiology of Painful Diabetic Neuropathy

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Abstract

Painful neuropathy is a common but inconsistent feature of chronic diabetes. Clinical studies have yet to offer robust clues to the pathogenesis of pain in diabetic patients, so there are no targeted prophylactic therapies. Interventions against established pain are restricted to drugs developed for other conditions that are frequently ineffective and can have prohibitive side effect profiles. Studies in diabetic rodents have identified a number of molecular and cellular disorders that may underlie the behavioral indices of pain seen in these models of diabetic neuropathy. Plausible mechanisms include over-expression of sensory receptors and ion channels in primary afferents that exaggerate or modify sensory input from the periphery and also amplification of sensory processing at the spinal cord level via sensitization and disinhibition mechanisms. There is also an emerging appreciation that the higher nervous system is not spared in diabetes, so that amplifier or generator sites for pain may be located within the brain and project pain sensations to the periphery. The developing appreciation of the pathogenesis of pain in animal models of diabetes has offered mechanistic validations for some therapies in current clinical use such as gabapentinoids, low-dose lidocaine, and alpha-lipoic acid while also highlighting new sites for intervention that may offer greater specificity and a reduced side effect profile.

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Acknowledgements 

Supported by NIH grant DK057629 (NAC) and a UC MEXUS-CONACYT Fellowship (TM-Z)

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Authors and Affiliations

  1. Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA

    Teresa Mixcoatl-Zecuatl Ph.D. & Nigel A. Calcutt Ph.D.

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  1. Teresa Mixcoatl-Zecuatl Ph.D.
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  2. Nigel A. Calcutt Ph.D.
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Correspondence to Nigel A. Calcutt Ph.D. .

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Editors and Affiliations

  1. , Department of Anesthesiology, University of California San Diego, Campus Point Dr 9300, La Jolla, 92037, California, USA

    Erin Lawson

  2. , Department of Neurology, University of Wisconsin, Highland Avenue 1685, Madison, 53705-2281, Wisconsin, USA

    Miroslav "Misha" Backonja

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Mixcoatl-Zecuatl, T., Calcutt, N.A. (2013). Biology and Pathophysiology of Painful Diabetic Neuropathy. In: Lawson, E., Backonja, M. (eds) Painful Diabetic Polyneuropathy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6299-6_2

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