Antinociceptive Interactions between Intrathecal Gabapentin and MK801 or NBQX in Rat Formalin Test.
10.3346/jkms.2005.20.2.307
- Author:
Myung Ha YOON
1
;
Hong Beom BAE
;
Jeong Il CHOI
Author Information
1. Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea. mhyoon@chonnam.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Antinociception;
gabapentin;
Drug Interactions;
Injections, Spinal;
MK801 Dizocilpine Maleate;
NBQX;
2,3-dioxo-6-nitro-7-sultamoylbenzo (f) quinoxaline
- MeSH:
Amines/administration & dosage/*pharmacology;
Analgesics/*pharmacology;
Animals;
Cyclohexanecarboxylic Acids/administration & dosage/*pharmacology;
Dizocilpine Maleate/*pharmacology;
Drug Interactions;
Excitatory Amino Acid Antagonists/*pharmacology;
Hyperalgesia/drug therapy;
Injections, Spinal;
Male;
Quinoxalines/*pharmacology;
Rats;
Rats, Sprague-Dawley;
Receptors, AMPA/drug effects/physiology;
Receptors, N-Methyl-D-Aspartate/drug effects/physiology;
Research Support, Non-U.S. Gov't;
gamma-Aminobutyric Acid/administration & dosage/*pharmacology
- From:Journal of Korean Medical Science
2005;20(2):307-312
- CountryRepublic of Korea
- Language:English
-
Abstract:
Antagonists for spinal N-methyl-D-aspartate (NMDA) and amino-hydroxy-methtyl-isoxazolepropionate (AMPA) receptors are effective in attenuating acute nociception or injury-induced hyperalgesia. The antinociception of spinal gabapentin is developed in injury-induced hyperalgesia without affecting acute nociception. The authors evaluated the effects of intrathecal gabapentin, NMDA antagonist (MK801) and AMPA antagonist (NBQX) in the formalin test which shows injury-induced hyperalgesia as well as acute pain. We further assessed the interactions between gabapentin and either MK801 or NBQX. Male Sprague-Dawley rats were implanted with intrathecal catheters. To evoke pain, 50 microliter of 5% formalin solution was injected into the hindpaw. The interaction was investigated by a fixed dose analysis or an isobolographic analysis. MK801 and NBQX suppressed flinching responses during phase 1 of the formalin test, while gabapentin had little effect on phase 1. All three agents decreased the phase 2 flinching response. A fixed dose analysis in phase 1 showed that gabapentin potentiated the antinociceptive effect of MK801 and NBQX. Isobolographic analysis in phase 2 revealed a synergistic interaction after coadministration of gabapentin-MK801 or gabapentin-NBQX. Correspondingly, spinal gabapentin with NMDA or AMPA antagonist may be useful in managing acute pain and injury-induced hyperalgesia.
