Evidence for suppression of spinal glial activation by dexmedetomidine in a rat model of monoarthritis.
1. Spinal glial cells play a key role in developing and maintaining allodynia and hyperalgesia following tissue inflammation. Dexmedetomidine, a highly selective α(2) -adrenoceptor (α(2) -AR) agonist, has exhibited a significant analgesic effect in various rodent models of chronic pain. However, whether spinal glial activation is involved in the analgesic effect of dexmedetomidine remains unknown. The present study investigated whether spinal administration of dexmedetomidine could antagonize glial activation in the spinal dorsal horn and attenuate thermal hyperalgesia in complete Freund's adjuvant (CFA)-induced ankle joint monoarthritic (MA) rats. 2. Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Repeated lumbar puncture (LP) administration of dexmedetomidine (10 μg) significantly attenuated MA-induced thermal hyperalgesia in a cumulative manner. Monoarthritis-induced spinal glial activation was also suppressed following dexmedetomidine application. The α(2A) -AR, essential for the antinociceptive effects of α(2) -AR agonists, was detected in spinal neurons and glia, as well as in dorsal root ganglion primary afferent neurons, which may be implicated in dexmedetomidine-induced suppression of spinal glial activation and antihyperalgesic effects. 3. These data provide the first evidence that blocking spinal glial activation is involved in the analgesic action of dexmedetomidine.
Xu
Bo
B
Department of Anaesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
Zhang
Wei-Shi
WS
Yang
Jia-Le
JL
Lû
Ning
N
Deng
Xiao-Ming
XM
Xu
Hua
H
Zhang
Yu-Qiu
YQ
D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006930:Hyperalgesia / Q000378:metabolism / Q000517:prevention & control; D007270:Injections, Intra-Articular; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D058647:Adrenergic alpha-2 Receptor Agonists; D020927:Dexmedetomidine; D005620:Freund's Adjuvant