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Korean Journal of Anesthesiology 2004;47(6):870-876.
DOI: https://doi.org/10.4097/kjae.2004.47.6.870   
Evaluation of the Interaction between Intrathecal 5-Hydroxytryptamine and Adenosine in the Formalin Test in a Rat Model.
Myung Ha Yoon, Hong Buem Bae, Jeong Il Choi
Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University, Gwangju, Korea. mhyoon@chonnam.ac.kr
Spinal 5-hydroxytryptamine (5-HT) and adenosine have been shown to display an antinociceptive effect. The authors evaluated the characteristics of this drug interaction after the concurrent delivery of 5-HT and adenosine in combination at the spinal level.
Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. Nociception was induced by subcutaneous injection of formalin solution (5%, 50microliter) into the hindpaw. Fixed dose analysis and isobolographic analysis were used to determine the properties of the interaction.
Intrathecal 5-HT dose-dependently suppressed the flinching response during phase 1 of the formalin test, whereas adenosine failed to affect the phase 1 flinching response. Both drugs attenuated the phase 2 flinching response in a dose-dependent manner. The intrathecal combination of 5-HT with a fixed dose of adenosine in phase 1 increased the antinociception of 5-HT alone, and isobolographic analysis in phase 2 revealed a synergistic interaction between intrathecal 5-HT and adenosine.
Intrathecal 5-HT reduced the facilitated pain state and acute pain. In contrast, intrathecal adenosine alone did not affect acute pain significantly, but attenuated the facilitated pain state. Furthermore, 5-HT interacted synergistically with adenosine at the spinal level. Thus, this combination may offer a potential remedy for the treatment of tissue injury pain.
Key Words: adenosine; formalin test; interaction; rat; serotonin; spinal cord


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