Anesth Analg 2004;98:1374-1379
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000107937.00902.FC
PAIN MEDICINE
Characteristic of Interactions Between Intrathecal Gabapentin and Either Clonidine or Neostigmine in the Formalin Test
Myung Ha Yoon, MD,
Jeong Il Choi, MD, and
Sang Hyun Kwak, MD
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea
Address correspondence and reprint requests to Myung Ha Yoon, MD, Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 8 Hakdong, Dongku, Gwangju 501–757, Korea. Address e-mail to mhyoon{at}chonnam.ac.kr
Intrathecal gabapentin is effective for phase 2 of the formalin response but not for acute pain. Unlike gabapentin, intrathecal clonidine and neostigmine attenuate both acute pain and phase 2 of the formalin response. We evaluated gabapentin’s interactions with either clonidine or neostigmine in the formalin test. Male Sprague-Dawley rats were used. For the formalin test, 50 µL of 5% formalin solution was injected into the hindpaw. The interaction of drugs was investigated by a fixed-dose analysis or an isobolographic analysis. Intrathecal gabapentin produced a suppression of the phase 2 flinching response, but not the phase 1 response, in the formalin test. Intrathecal clonidine and neostigmine resulted in a reduction of the pain behavior in both phases. A fixed-dose analysis in phase 1 showed that gabapentin potentiated the antinociceptive effect of clonidine and neostigmine. An isobolographic analysis in phase 2 revealed a synergistic interaction after intrathecal administration of gabapentin-clonidine or gabapentin-neostigmine mixture. We conclude that the combination of gabapentin with either clonidine or neostigmine at the level of the spinal cord could play a major role not only in acute pain, but also in phase 2 of the formalin response.
IMPLICATIONS: We determined the pharmacological properties of gabapentin combined with either clonidine or neostigmine in the formalin test. Spinal gabapentin reinforced the effects of clonidine and neostigmine in the formalin test. The hitherto unreported action of gabapentin on acute nociceptive stimulus could be of considerable significance.
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