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ANALGESIA

The Characteristics of Intravenous Adenosine-Induced Antinociception in a Rabbit Model of Acute Nociceptive Pain: A Comparative Study with Remifentanil

Masakazu Hayashida, MD, PhD^*, Atsuo Fukunaga, MD, PhD, Ken-ichi Fukuda, DDS, Satoru Sakurai, DDS, Hideki Mamiya, DDS, Tatsuya Ichinohe, DDS, PhD, Yuzuru Kaneko, DDS, PhD, and Kazuo Hanaoka, MD, PhD

From the *Surgical Center, Research Hospital, Institute of Medical Institute, The University of Tokyo, Tokyo, Japan; Department of Anesthesiology, University of California, Los Angeles, California; Department of Anesthesiology, Tokyo Dental College; and Department of Anesthesiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Address correspondence to Masakazu Hayashida, Surgical Center Research Hospital, Institute of Medical Institute, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo 108-8639, Japan. Address e-mail to hayashida-todai{at}umin.ac.jp.

Abstract

BACKGROUND: Adenosine and remifentanil are potent IV analgesics with ultrashort half-lives. The antinociceptive effect of IV adenosine has not been clearly characterized. We compared the antinociceptive effects of adenosine and remifentanil in rabbits.

METHODS: Sixteen rabbits, placed on a sling allowing reasonably free movement, received IV adenosine (400 µg · kg^–1 · min^–1) or remifentanil (0.4 µg · kg^–1 · min^–1) over 240 min.

RESULTS: Both drugs produced profound antinociception, as assessed by the number of animals unresponsive to clamping the forepaw and the electrical stimulation threshold of escape movement. With remifentanil, the antinociceptive effect increased rapidly, reaching its peak at 60 min, and then began to decline despite continued infusion. After stopping the infusion, it decreased rapidly and disappeared within 30 min. The vasodilating effect of IV adenosine was immediate in onset and ultrashort in duration. The antinociceptive effect of adenosine increased slowly but progressively during the infusion, reaching its peak only when the infusion ended. Then it decreased slowly over the following 360 min after terminating the infusion.

CONCLUSION: Remifentanil had a rapid onset and short duration of action, and probably showed signs of tolerance development, whereas the antinocieptive effect of adenosine was slow in onset and long-lasting, despite its ultrashort plasma half-life and the immediate on–off profiles of its vasodilating effect.