Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan;39(1):e14729.
doi: 10.1111/dme.14729. Epub 2021 Oct 28.

Painful diabetic peripheral neuropathy: Role of oxidative stress and central sensitisation

Affiliations
Review

Painful diabetic peripheral neuropathy: Role of oxidative stress and central sensitisation

Di Ye et al. Diabet Med. 2022 Jan.

Abstract

Aims: Diabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear. There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain.

Methods: We reviewed literature in PubMed published between January 2005 and August 2021.

Results and conclusions: In diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment.

Keywords: central sensitisation; diabetic peripheral neuropathy; oxidative stress; pain; pain modulation.

PubMed Disclaimer

References

REFERENCES

    1. Román-Pintos LM, Villegas-Rivera G, Rodríguez-Carrizalez AD, Miranda-Díaz AG, Cardona-Muñoz EG. Diabetic polyneuropathy in type 2 diabetes mellitus: inflammation, oxidative stress, and mitochondrial function. Journal of Diabetes Research. 2016;2016:3425617. doi:10.1155/2016/3425617
    1. Ziegler D. Diabetic peripheral and autonomic neuropathy. In: Holt RIG, Cockram CS, Flyvbjerg A, Goldstein BJ, eds. Textbook of Diabetes, 5th ed. Wiley-Blackwell; 2017:580-608. doi:10.1002/9781118924853
    1. Ringkamp M, Raja SN, Campbell JN, Meyer RA. Peripheral mechanisms of cutaneous nociception. In: McMahon SB, Koltzenburg M, Tracey I, Turk D, eds. Wall and Melzack’s Textbook of Pain, 6th ed. Elsevier/Saunders; 2013:1-30.
    1. Calcutt NA. Diabetic neuropathy and neuropathic pain: a (con)fusion of pathogenic mechanisms? Pain. 2020;161(Suppl 1):S65-S86. doi:10.1097/j.pain.0000000000001922
    1. Albers JW, Herman WH, Pop-Busui R, et al. Effect of prior intensive insulin treatment during the diabetes control and complications trial (DCCT) on peripheral neuropathy in type 1 diabetes during the epidemiology of diabetes interventions and complications (EDIC) study. Diabetes Care. 2010;33(5):1090-1096. doi:10.2337/dc09-1941

Publication types

MeSH terms

LinkOut - more resources