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Korean J Anesthesiol. 2004 Dec;47(6):870-876. Korean. Original Article.
Yoon MH , Bae HB , Choi JI .
Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University, Gwangju, Korea.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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