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Eur J Pain. 2014 Feb;18(2):162-73. doi: 10.1002/j.1532-2149.2013.00356.x. Epub 2013 Jul 19.

Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats.

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Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; Department of Anesthesiology, Kaohsiung Medical University Hospital, Taiwan.



In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys-regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates microglia in the spinal dorsal horn (SDH). However, information on diabetes-induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain.


Sixty-six rats were divided into diabetic and control groups: control rats (n = 18; 1 mL of normal saline via the right femoral vein) and diabetic rats [n = 48; 60 mg/kg streptozotocin (STZ) via the right femoral vein]. Hindpaw behavioural tests, Navs expression in the DRG, activation of glial cells in the SDH and the number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6 months following saline and STZ administration.


All diabetic rats exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased withdrawal threshold to mechanical stimuli but had blunted responses to thermal stimuli. Consistent up-regulation of Nav1.3 and down-regulation of Nav1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, Nav1.3 and microglial activation was observed. In addition, microglia activation in the SDH of STZ-induced diabetes was mediated, in part, by phosphorylation of p-38 mitogen-activated protein kinase.


Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia.

[Indexed for MEDLINE]

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