Intrathecal landiolol inhibits nociception and spinal c-Fos expression in the mouse formalin test

Abstract

Purpose: The purpose of this study was to determine if intrathecal landiolol, a β1-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·kg-1, 500 μg·kg-1 and 750 μ·gkg-1 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 1(0-10 min) and phase 11(10-45 min). The c-Fos protein expressions in the spinal dorsal horn were detected with immunohistochemical techniques in the control and landiolol 750 μg·kg-1 groups. Results: Compared to the control group, intrathecal injection of landiolol 750 μg·kg-1 significantly decreased pain-related behaviours in phase I, while intrathecal landiolol 250 μg·kg-1, 500 μg·kg-1 and 750 μg·kg-1 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·kg-1 group compared to the control group (landiolol 750 μg·kg-1 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 β 1-adrenoreceptors in spinal nociceptive processing.