Korean J Anesthesiol.  2004 Dec;47(6):870-876. 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

• Yoon MH
• Bae HB
• Choi JI

• KMID: 2032605
• DOI: http://doi.org/10.4097/kjae.2004.47.6.870

Abstract

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.

Keyword

adenosine; formalin test; interaction; rat; serotonin; spinal cord

MeSH Terms

Acute Pain
Adenosine*
Animals
Catheters
Drug Interactions
Formaldehyde*
Humans
Injections, Subcutaneous
Male
Models, Animal*
Nociception
Pain Measurement*
Rats*
Rats, Sprague-Dawley
Serotonin*
Spinal Cord
Adenosine
Formaldehyde
Serotonin