Dexmedetomidine prevents remifentanil-induced postoperative hyperalgesia and decreases spinal tyrosine phosphorylation of N-methyl-d-aspartate receptor 2B subunit.
Numerous studies have demonstrated that prolonged opioid exposure can enhance pain sensitivity that presents as opioid-induced hyperalgesia (OIH). Activation of spinal α2-adrenergic receptor may play an important role in the development of OIH. Dexmedetomidine is an α2-adrenergic agonist that has been shown to synergize with opioids. The aim of this study was to investigate the antihyperalgesia effects of dexmedetomidine on remifentanil-induced postinfusion hyperalgesia in a rat model of incision pain. We also evaluated whether the antihyperalgesic effects of dexmedetomidine were associated with suppression of NMDAR excitability, as measured by a reduction in spinal cord NR2B phosphorylation. Dexmedetomidine (12.5 μg/kg, 25 μg/kg, 50 μg/kg) was administered subcutaneously 30 min before plantar incision. Pretreatment with dexmedetomidine significantly decreased remifentanil-induced hyperalgesia, as indicated by increased paw withdrawal latencies and thresholds to thermal and mechanical stimulation respectively. Correlated with the pain behavior changes, Western blotting experiments also revealed that dexmedetomidine could decrease NR2B subunit phosphorylation (Tyr1472 site) in the dorsal horn, which was upregulated after remifentanil infusion. These results suggest that dexmedetomidine can efficiently alleviate OIH and it may be an effective novel option for the treatment of OIH. Our data also provide evidence that dexmedetomidine's anti-hyperalgesic effect may depend on its ability to modulate spinal cord NMDAR activation via suppression of NR2B phosphorylation.
Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China.
YaGuo
Y
Zheng
SongQing
S
Cui
Yue
Y
Liu
Juan
J
Zhang
Wei
W
Zhang
Jing
J
Zhang
XiaoPing
X
Gu
ZhengLiang
Z
Ma
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D020927:Dexmedetomidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D010149:Postoperative Pain / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000077208:Remifentanil; D013116:Spinal Cord / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D014443:Tyrosine; D020927:Dexmedetomidine; D000077208:Remifentanil