Dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of monoarthritis.
OBJECTIVE
To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor (alpha(2)AR) agonist, on thermal hyperalgesia and spinal glial activation evoked by monoarthritis (MA).


METHODS
MA was induced by an intra-articular injection of complete Freund's adjuvant (CFA). Thermal hyperalgesia was measured by Hargreaves' test. The spinal glial activation status was analyzed by GFAP (an astrocytic marker) and Iba-1 (a microglial marker) immunohistochemistry or immunoblotting.


RESULTS
Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal (ip) injection of dexmedetomidine (2.5 and 10 microg/kg) was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 microg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed.


CONCLUSIONS
Systemic dexmedetomidine inhibits the activation of spinal glia, which is possibly associated with its antihyperalgesia in monoarthritic rats.
Xu
Bo
B
Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
Zhang
Wei-shi
WS
Yang
Jia-le
JL
Xu
Hua
H
Deng
Xiao-ming
XM
Zhang
Yu-qiu
YQ
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000627:therapeutic use*; D005620:Freund's Adjuvant; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D020927:Dexmedetomidine; D005620:Freund's Adjuvant