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.

Abstract

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.

• Authors: Ming Jiang, Wei Zhang, Zhengliang Ma, Xiaoping Gu
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 112 Pg. 56-63 (Nov 2013) ISSN: 1873-5177 [Electronic] United States
• PMID: 24076088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Analgesics
• NR2B NMDA receptor
• Phenols
• Piperidines
• Receptors, N-Methyl-D-Aspartate
• Ro 25-6981
• Tyrosine

Topics

• Analgesics (pharmacology)
• Animals
• Blotting, Western
• Hyperalgesia (prevention & control)
• Injections, Spinal
• Male
• Phenols (pharmacology)
• Phosphorylation
• Piperidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, metabolism)
• Tyrosine (metabolism)