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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
Author(s) -
Cheng K.I.,
Wang H.C.,
Chuang Y.T.,
Chou C.W.,
Tu H.P.,
Yu Y.C.,
Chang L.L.,
Lai C.S.
Publication year - 2014
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2013.00356.x
Subject(s) - medicine , streptozotocin , endocrinology , microglia , neuropathic pain , dorsal root ganglion , diabetes mellitus , allodynia , diabetic neuropathy , p38 mitogen activated protein kinases , protein kinase a , saline , hyperalgesia , kinase , receptor , anesthesia , inflammation , chemistry , nociception , dorsum , anatomy , biochemistry
Background In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys‐regulated sodium channel ( N avs) 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 N avs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain. Methods 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, N avs 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. Results 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 N av1.3 and down‐regulation of N av1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, N av1.3 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. Conclusions Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of N av1.3 and increased p38 phosphorylation in activated microglia.