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Antinociceptive Interactions between Intrathecal Gabapentin and MK801 or NBQX in Rat Formalin Test

Yoon, Myung Ha    (Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea.   ); Bae, Hong Beom    (Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea.   ); Choi, Jeong Il    (Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea.  );
  • 초록

    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 μL 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.


  • 주제어

    Antinociception .   gabapentin .   Drug Interactions .   Injections, Spinal .   MK801 Dizocilpine Maleate .   NBQX .   2,3-dioxo-6-nitro-7-sultamoylbenzo (f) quinoxaline.  

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