TY - JOUR
T1 - Neurons and microglia; a sickly-sweet duo in diabetic pain neuropathy
AU - Rajchgot, Trevor
AU - Thomas, Sini Christine
AU - Wang, Jo Chiao
AU - Ahmadi, Maryam
AU - Balood, Mohammad
AU - Crosson, Théo
AU - Dias, Jenny Pena
AU - Couture, Réjean
AU - Claing, Audrey
AU - Talbot, Sébastien
N1 - Funding Information:
This project has been made possible by the Canada Research Chair program (#950-231859) and the Brain Canada Foundation (ST) through the Canada Brain Research Fund, with the financial support of Health Canada and the Azrieli Foundation.
Publisher Copyright:
Copyright © 2019 Rajchgot, Thomas, Wang, Ahmadi, Balood, Crosson, Dias, Couture, Claing and Talbot.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Diabetes
KW - Hyperglycemia
KW - Microglia
KW - Neurons
KW - Neuropathy
KW - Oxidative stress
KW - Pain
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U2 - 10.3389/fnins.2019.00025
DO - 10.3389/fnins.2019.00025
M3 - Review article
C2 - 30766472
AN - SCOPUS:85065506784
SN - 1662-4548
VL - 13
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
IS - JAN
M1 - 25
ER -