Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain.

The Journal of Physiology
Nikita VedRichard Phillip Hulse

Abstract

Diabetes is thought to induce neuropathic pain through activation of dorsal horn sensory neurons in the spinal cord. Here we explore the impact of hyperglycaemia on the blood supply supporting the spinal cord and chronic pain development. In streptozotocin-induced diabetic rats, neuropathic pain is accompanied by a decline in microvascular integrity in the dorsal horn. Hyperglycaemia-induced degeneration of the endothelium in the dorsal horn was associated with a loss in vascular endothelial growth factor (VEGF)-A165 b expression. VEGF-A165 b treatment prevented diabetic neuropathic pain and degeneration of the endothelium in the spinal cord. Using an endothelial-specific VEGFR2 knockout transgenic mouse model, the loss of endothelial VEGFR2 signalling led to a decline in vascular integrity in the dorsal horn and the development of hyperalgesia in VEGFR2 knockout mice. This highlights that vascular degeneration in the spinal cord could be a previously unidentified factor in the development of diabetic neuropathic pain. Abnormalities of neurovascular interactions within the CNS of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network withi...Continue Reading

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Citations

Aug 30, 2018·The Journal of Physiology·Madhavi Jere, Ryan M Cassidy
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May 20, 2020·The Journal of Clinical Investigation·Zoe L GrantLeigh Coultas
Oct 16, 2021·Journal of Experimental & Clinical Cancer Research : CR·Laura MicheliLorenzo Di Cesare Mannelli
Oct 22, 2021·Diabetic Medicine : a Journal of the British Diabetic Association·Di YePeter D Drummond

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