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From the Department of Anaesthesiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Address correspondence to: Dr. Satoshi Kashimoto, Associate Professor, 1110 Shimokato, Chuo, Yamanashi, Japan 409-3898. Phone: +81-55-2739690; Fax: +81-55-2736755; E-mail: satoshik{at}yamanashi.ac.jp
Purpose: The purpose of this study was to determine if intrathecal landiolol, a ß1-blocker, can modulate formalin-induced nociception and spinal c-Fos expression in mice, in the absence of anesthesia.
Methods: Thirty-two mice were randomly assigned to one of four groups: the control group (n = 8) received intrathecal normal saline 10 µL, while the other three groups (n = 8 for each) received intrathecal landiolol at escalating doses of 250 µg·kg1, 500 µg·kg1 and 750 µg·kg1 respectively, immediately after induction of anesthesia with isoflurane. After awakening, inflammatory pain was induced by 10 µL of 5% formalin solution injected into the dorsal surface of the right hind paw. The nociceptive behaviours including licking, biting and lifting of the injected paw were cumulatively recorded as seconds of behaviours/min during phase I (010 min) and phase II (1045 min). The c-Fos protein expressions in the spinal dorsal horn were detected with immunohistochemical techniques in the control and landiolol 750 µg·kg1 groups.
Results: Compared to the control group, intrathecal injection of landiolol 750 µg·kg1 significantly decreased pain-related behaviours in phase I, while intrathecal landiolol 250 µg·kg1, 500 µg·kg1 and 750 µg·kg1 significantly decreased pain-related behaviours in phase II during the formalin test. The numbers of c-Fos immunoreactive nuclei in the L5 spinal dorsal horn were significantly lower in the landiolol 750 µg·kg1 group compared to the control group (landiolol 750 µg·kg1 2.4 ± 1.1 vs control 9.2 ± 3.9; P < 0.01).
Conclusion: The present study indicates that intrathecally administered landiolol produces significant antinociceptive effects in the formalin test. Although further studies exploring the detailed mechanism are needed, these data suggest a potential role of ß1-adrenoreceptors in spinal nociceptive processing.
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