Intrathecal adenosine enhances the antinociception of Xylazine in goats

Mahmoud M Abouelfetouh; Eman Salah; Lingling Liu; Mingxing Ding; Yi Ding

doi:10.1186/s12917-022-03193-9

Intrathecal adenosine enhances the antinociception of Xylazine in goats

BMC Vet Res. 2022 Mar 17;18(1):105. doi: 10.1186/s12917-022-03193-9.

Authors

Mahmoud M Abouelfetouh^{1

2}, Eman Salah^{3

4}, Lingling Liu^{1

5}, Mingxing Ding¹, Yi Ding⁶

Affiliations

¹ College of Veterinary Medicine, Huazhong Agricultural University, No.1, Shizishan Street, Hongshan District, Wuhan, 430070, Hubei Province, China.
² Department of Surgery, Radiology and Anaesthesiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, 13736, Egypt.
³ National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, 430070, Hubei Province, China.
⁴ Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, 13736, Egypt.
⁵ Clinical Veterinary Laboratory, College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan Province, China.
⁶ College of Veterinary Medicine, Huazhong Agricultural University, No.1, Shizishan Street, Hongshan District, Wuhan, 430070, Hubei Province, China. dingyi@mail.hzau.edu.cn.

Abstract

Background: The role of adenosine (AD) in neuromodulation of nociceptive signaling at the level of the spinal cord has been established in both preclinical and clinical models. Recently, the signaling pathway that involves adenosine 5-monophosphate activated protein kinase has been reported to mediate the antinociceptive effects of xylazine (XYL). The objective of this study was to investigate the antinociceptive, cardiorespiratory and hematological effects of intrathecal administration of combined XYL-AD in goats as compared to XYL alone. Six clinically healthy adult goats weighing 25 ± 2 kg were randomly assigned to one of three groups in a cross-over design. Goats were sedated with XYL (0.05 mg/kg, IM) in all groups. Ten min later, 0.9% saline solution [SAL group], XYL (0.05 mg/kg) [XYL group] or a combination of XYL (0.05 mg/kg) and AD (2000 µg) [XYL-AD group] was injected intrathecally. Antinociception scores and both cardiorespiratory and hematological parameters were measured before XYL sedation and intrathecal injection (baseline), and at 5, 10, 15, 30, 60, 90, 120 and 150 min thereafter.

Results: The XYL-AD group showed significantly earlier onset of antinociception [5 (5-7) min] than XYL [13 (12-14.25] min (P = 0.031). The duration of complete antinociception in goats that received XYL-AD was significantly longer (P = 0.031) than that received XYL alone [65 (58.75-66.25) and 47.5 (43.75-51.25) min, respectively]. In both XYL and XYL-AD groups, heart rate (HR), arterial blood pressure (SAP, MAP and DAP) were significantly decreased (P < 0.05) compared to the baseline. Compared to the SAL group, a statistically significant reduction in HR from 10 to 150 min (P < 0.05) was detected in the XYL group contrary to the XYL-AD group. Differences in the hematological parameters among different groups were insignificant.

Conclusions: AD injected intrathecally interacts synergistically with XYL to promote antinociception in goats. This discovery supports the use of AD in combination with XYL in clinical trials.

Keywords: Adenosine; Antinociception; Cardiorespiratory parameters; Goats; Xylazine.

Publication types

Randomized Controlled Trial, Veterinary

MeSH terms

Adenosine / pharmacology
Animals
Cross-Over Studies
Goats*
Heart Rate
Xylazine* / pharmacology

Substances

Xylazine
Adenosine

Abstract

Publication types

MeSH terms

Substances

Grants and funding