Systemic dexmedetomidine attenuates mechanical allodynia through extracellular sign db type 2 diabetic mice.
Neurosci Lett
; 657: 126-133, 2017 Sep 14.
Article
in En
| MEDLINE
| ID: mdl-28757391
ABSTRACT
Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus. However, the treatment for PDN is limited in clinical practice. In the present study, we investigated the effect of systemic administration dexmedetomidine (DEX), a selective alpha 2 adrenergic receptor (α2AR) agonist, on mechanical allodynia and its underlying mechanism in db/db mice, an animal model of type 2 diabetes mellitus. Our data demonstrated that db/db mice develop mechanical allodynia at the early stage of diabetes. During the period of mechanical allodynia, we detected increased release of norepinephrine (NE) and decreased levels of α2A-Adrenoceptors in db/db mice. Immunohistochemistry showed that the α2A-Adrenoceptor is predominantly expressed in neurons in the spinal cord. Acute injection of dexmedetomidine significantly decreased mechanical allodynia, which was blocked by its selective antagonist BRL44408. Furthermore, the upregulation of pERK1 and pERK2 in db/db mice were attenuated by preadministration of dexmedetomidine. We provide the first evidence that the functional alternation of spinal noradrenergic system might underlie exaggerated nociception in PDN. Systemic dexmedetomidine inhibits the mechanical allodynia which is related to ERK signaling pathway in type 2 diabetes, implying that the α2-Adrenoceptor might be a potential therapeutic strategy for PDN.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dexmedetomidine
/
MAP Kinase Signaling System
/
Diabetes Mellitus, Experimental
/
Diabetes Mellitus, Type 2
/
Diabetic Neuropathies
/
Adrenergic alpha-2 Receptor Agonists
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Hyperalgesia
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Neurosci Lett
Year:
2017
Document type:
Article
Affiliation country:
China