The Non-NMDA Glutamate Receptor Antagonist CNQX Augments Lidocaine Antinociception Through a Spinal Action in Rats

Autor: Yoshihiro Kosaka, Kaoru Hara, Yoji Saito, Noritaka Imamachi, Shinichi Sakura
Rok vydání: 1999
Předmět:
Zdroj: Anesthesia & Analgesia. 89:416-421
ISSN: 0003-2999
Popis: Non-NMDA glutamate receptor antagonists produce antinociceptive effects, but the antinociceptive interaction between non-NMDA glutamate receptor antagonists and local anesthetics has not been demonstrated. We designed this study to evaluate the antinociceptive effects of a non-NMDA glutamate receptor antagonist and its interaction with lidocaine in rats. Intrathecal catheters were implanted at the L4-5 level in rats. The tail flick (TF) and colorectal distension (CD) tests were used to assess somatic and visceral antinociceptive effects, respectively. The TF latency and CD threshold were measured before and for 180 min after the intrathecal administration of lidocaine (20-100 [micro sign]g), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (0.4-4.0 [micro sign]g), a combination of CNQX (0.2-0.6 [micro sign]g) and lidocaine (10-30 [micro sign]g), or isotonic sodium chloride solution. The TF latency and CD threshold were converted to the percent maximal possible effect (%MPE). To determine synergistic interaction, isobolographic analysis was used. Lidocaine or CNQX increased %MPEs in both the TF and CD tests. The coadministration of CNQX 0.4 [micro sign]g and lidocaine 20 [micro sign]g, which had no effect by alone, significantly increased %MPEs in the TF and CD tests for 30 min and 10 min, respectively. Isobolographic analysis revealed the synergistic antinociception of CNQX and lidocaine in the TF test. Motor impairment was not observed after that combination. We conclude that CNQX and lidocaine produce synergistic analgesia on somatic and visceral pain at the spinal level. Implications: We investigated the antinociceptive effects of 6-cyano-7-nitroquinoxaline-2,3-dione and its interaction with lidocaine at the spinal level in rats. Intrathecal 6-cyano-7-nitroquinoxaline-2,3-dione produced both somatic and visceral antinociception, and its coadministration with lidocaine showed synergistic antinociceptive effects. (Anesth Analg 1999;89:416-21)
Databáze: OpenAIRE