Neurons and microglia; a sickly-sweet duo in diabetic pain neuropathy

Trevor Rajchgot, Sini Christine Thomas, Jo Chiao Wang, Maryam Ahmadi, Mohammad Balood, Théo Crosson, Jenny Pena Dias, Réjean Couture, Audrey Claing, Sébastien Talbot

Research output: Contribution to journalReview article

Abstract

Diabetes is a common condition characterized by persistent hyperglycemia. High blood sugar primarily affects cells that have a limited capacity to regulate their glucose intake. These cells include capillary endothelial cells in the retina, mesangial cells in the renal glomerulus, Schwann cells, and neurons of the peripheral and central nervous systems. As a result, hyperglycemia leads to largely intractable complications such as retinopathy, nephropathy, hypertension, and neuropathy. Diabetic pain neuropathy is a complex and multifactorial disease that has been associated with poor glycemic control, longer diabetes duration, hypertension, advanced age, smoking status, hypoinsulinemia, and dyslipidemia. While many of the driving factors involved in diabetic pain are still being investigated, they can be broadly classified as either neuron -intrinsic or -extrinsic. In neurons, hyperglycemia impairs the polyol pathway, leading to an overproduction of reactive oxygen species and reactive nitrogen species, an enhanced formation of advanced glycation end products, and a disruption in Na+/K+ ATPase pump function. In terms of the extrinsic pathway, hyperglycemia leads to the generation of both overactive microglia and microangiopathy. The former incites a feed-forward inflammatory loop that hypersensitizes nociceptor neurons, as observed at the onset of diabetic pain neuropathy. The latter reduces neurons' access to oxygen, glucose and nutrients, prompting reductions in nociceptor terminal expression and losses in sensation, as observed in the later stages of diabetic pain neuropathy. Overall, microglia can be seen as potent and long-lasting amplifiers of nociceptor neuron activity, and may therefore constitute a potential therapeutic target in the treatment of diabetic pain neuropathy.

Original languageEnglish (US)
Article number25
JournalFrontiers in Neuroscience
Volume13
Issue numberJAN
DOIs
StatePublished - Jan 1 2019

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Diabetic Neuropathies
Microglia
Neurons
Pain
Hyperglycemia
Nociceptors
Hypertension
Reactive Nitrogen Species
Glucose
Advanced Glycosylation End Products
Mesangial Cells
Schwann Cells
Peripheral Nervous System
Dyslipidemias
Blood Glucose
Retina
Reactive Oxygen Species
Central Nervous System
Endothelial Cells
Smoking

Keywords

  • Diabetes
  • Hyperglycemia
  • Microglia
  • Neurons
  • Neuropathy
  • Oxidative stress
  • Pain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Rajchgot, T., Thomas, S. C., Wang, J. C., Ahmadi, M., Balood, M., Crosson, T., ... Talbot, S. (2019). Neurons and microglia; a sickly-sweet duo in diabetic pain neuropathy. Frontiers in Neuroscience, 13(JAN), [25]. https://doi.org/10.3389/fnins.2019.00025

Neurons and microglia; a sickly-sweet duo in diabetic pain neuropathy. / Rajchgot, Trevor; Thomas, Sini Christine; Wang, Jo Chiao; Ahmadi, Maryam; Balood, Mohammad; Crosson, Théo; Pena Dias, Jenny; Couture, Réjean; Claing, Audrey; Talbot, Sébastien.

In: Frontiers in Neuroscience, Vol. 13, No. JAN, 25, 01.01.2019.

Research output: Contribution to journalReview article

Rajchgot, T, Thomas, SC, Wang, JC, Ahmadi, M, Balood, M, Crosson, T, Pena Dias, J, Couture, R, Claing, A & Talbot, S 2019, 'Neurons and microglia; a sickly-sweet duo in diabetic pain neuropathy', Frontiers in Neuroscience, vol. 13, no. JAN, 25. https://doi.org/10.3389/fnins.2019.00025
Rajchgot T, Thomas SC, Wang JC, Ahmadi M, Balood M, Crosson T et al. Neurons and microglia; a sickly-sweet duo in diabetic pain neuropathy. Frontiers in Neuroscience. 2019 Jan 1;13(JAN). 25. https://doi.org/10.3389/fnins.2019.00025
Rajchgot, Trevor ; Thomas, Sini Christine ; Wang, Jo Chiao ; Ahmadi, Maryam ; Balood, Mohammad ; Crosson, Théo ; Pena Dias, Jenny ; Couture, Réjean ; Claing, Audrey ; Talbot, Sébastien. / Neurons and microglia; a sickly-sweet duo in diabetic pain neuropathy. In: Frontiers in Neuroscience. 2019 ; Vol. 13, No. JAN.
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