Antinociception and prevention of hyperalgesia by intrathecal administration of Ro 25-6981, a highly selective antagonist of the 2B subunit of N-methyl-D-aspartate receptor.
BACKGROUND
NR2B subunits (NMDA receptor 2B subunit) play an important role in generation of pain and forming central sensitization of pain. Ro 25-6981, a highly selective NR2B antagonist, gained much attention in recent years. In this study, we used a rat model of incisional pain to investigate effects of postoperative analgesia and changes of postoperative hyperalgesia induced by remifentanil through the pretreatment of intrathecal administration with Ro 25-6981.


METHODS
The behavioral changes of rats have been evaluated by the paw withdrawal mechanical threshold and paw withdrawal thermal latency after intrathecal injection of Ro 25-6981. The expression of NR2B with tyrosine phosphorylation in the spinal dorsal horn was analyzed by Western blotting.


RESULTS
Intrathecal injection of Ro 25-6981 significantly enhanced the paw withdrawal mechanical threshold and paw withdrawal thermal latency after the operation. Significant change has been observed after intrathecal injection of 800.0 μg of Ro 25-6981 and at 2h after operation in the oblique pull test degree and BBB rating score. Pretreatment of Ro 25-6981 decreased the high level expression of NR2B with tyrosine phosphorylation in spinal dorsal horn of the rat model after the operation.


CONCLUSIONS
Intrathecal injection of Ro 25-6981 had significant analgesic effects on incision pain in rats and effectively attenuated postoperative hyperalgesia induced by remifentanil.
Department of Anesthesiology, Drum Tower Hospital, Medical Department of Nanjing University, Nanjing, 210008 Jiangsu Province, PR China.
Ming
M
Jiang
Wei
W
Zhang
Zhengliang
Z
Ma
Xiaoping
X
Gu
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D006930:Hyperalgesia / Q000517:prevention & control*; D007278:Injections, Spinal; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000700:Analgesics; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D014443:Tyrosine
Antinociception; Hyperalgesia; Intrathecal administration; N-methyl-d-aspartate receptor; Prevention; Ro 25-6981