Antinociceptive effect of intrathecally applied alpha2 agonists (xylazine and detomidine) in sheep and the response to atipamezole

This study evaluated the antinociceptive and physiologic effects of xylazine (X) and detomidine (D) administered intrathecally (IT) at the lumbosacral space, before and after the injection of atipamezole (A) IV. The study was approved by the National Animal Protection Authorities. Five adult healthy female sheep were anaesthetized with propofol on four occasions to inject the following treatments IT: groups 1 and 2, 0.05 mg kg^?1 X (2 mg mL^?1 saline) IT; groups 3 and 4, 0.01 mg kg^?1 D (0.5 mg mL^?1 saline) IT ( Waterman et al. 1988 ). Nociceptive threshold (TH) was tested by applying pulsed and stepwise enhanced direct current ( Ludbrook et al. 1995 ) at one hind leg pastern and noting the current at the moment of foot lift. Maximum current applied was 40 mA. Baseline TH was measured twice before anaesthesia and every 10 minutes when the sheep regained consciousness. Atipamezole was given IV immediately after reaching maximum analgesic action of X and D as defined by two equal or decreasing TH values and measurements were continued for 90 minutes. The dose of A for groups 1 and 3 was 0.005 mg kg^?1 (0.25 mg mL^?1 saline) IV, and for groups 2 and 4 was 0.0025 mg kg^?1 A (0.25 mg mL^?1 saline) IV. Heart rate (HR), mean direct arterial pressure (MAP), PaO₂ and PaCO₂ were measured. The differences between measurements recorded before and after treatment were analysed using a paired t‐test for the drug effects and a nonparametric Wilcoxon's rank sum test for the comparison between groups. A p‐value < 0.05 was considered significant. All sheep were able to stand before A IV. Threshold baseline value was 4.5 ± 1.7 (mean ± SD) mA for all animals. Xylazine caused a significantly higher TH rise (35.2 ± 1.8 mA), faster onset (21.1 ± 16.0 minutes) and longer duration of the TH enhancement (104.1 ± 8.6 minutes) than D (TH: 16.3 ± 7.8 mA, onset: 49.5 ± 28.4 minutes, duration: 59.3 ± 27.3 minutes). A significant increase in PaCO₂ was observed in the X and D treated animals, 0.39 ± 0.21 kPa (2.9 ± 1.6 mm Hg) and 0.39 ± 0.29 kPa (2.9 ± 2.2 mm Hg), respectively. Heart rate was significantly decreased by ?21 ± 17 beats minute^?1 for X animals and ?13 ± 13 beats minute^?1 for D. Mean arterial pressure (?9 ± 13 mm Hg for X and ?1 ± 11 mm Hg for D animals) and PaO₂ 0.65 ± 1.32 kPa (4.9 ± 9.9 mm Hg) for X and 1.45 ± 4.19 kPa (10.9 ± 31.4 mm Hg) for D animals) did not change significantly. The nociceptive threshold was not affected by A in any group. Threshold values of all X treated animals before A was 39.3 ± 1.4 mA and after was 37.2 ± 6.3 (group 1) and 40 ± 0 (group 2). Threshold values of all D treated animals before A was 21.0 ± 8.3 and after was 19.4 ± 7.3 (group 3) and 24.8 ± 8.0 (group 4). At the dosages administered intrathecally in this study, X and to a lower degree D induce antinociception without major physiologic changes. Atipamezole up to 0.005 mg kg^?1 IV does not affect the resulting antinociception as assessed by electrical stimulation.