Antiemetic effects of baclofen in a shrew model of postoperative nausea and vomiting: Whole‐transcriptome analysis in the nucleus of the solitary tract

• Published in: CNS neuroscience & therapeutics Vol. 28; no. 6; pp. 922 - 931
• Main Authors: Konno, Daisuke, Sugino, Shigekazu, Shibata, Tomoko F, Misawa, Kazuharu, Imamura‐Kawasawa, Yuka, Suzuki, Jun, Kido, Kanta, Nagasaki, Masao, Yamauchi, Masanori
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2022; John Wiley and Sons Inc
• Subjects: Abdomen; Abdominal surgery; Anesthesia; Animal models; Animals; Antiemetics - therapeutic use; Baclofen; Baclofen - pharmacology; Baclofen - therapeutic use; Behavior; Brain research; Emetics; Female; GABAB receptor‐mediated signaling pathway; Gene expression; Gene Expression Profiling; Genomes; Laboratory animals; Nausea; nucleus of the solitary tract; Original; postoperative nausea and vomiting; Postoperative Nausea and Vomiting - drug therapy; Shrews - physiology; Signal transduction; Solitary Nucleus; Solitary tract nucleus; Soricidae; Surgery; Sutures; Transcriptomes; Vomiting; Vomiting - drug therapy; Vomiting - prevention & control; whole‐transcriptome analysis; γ-Aminobutyric acid B receptors; Germany; GABAB receptor-mediated signaling pathway; whole-transcriptome analysis; nucleus of the solitary tract; postoperative nausea and vomiting
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.13823

Aims The molecular genetic mechanisms underlying postoperative nausea and vomiting (PONV) in the brain have not been fully elucidated. This study aimed to determine the changes in whole transcriptome in the nucleus of the solitary tract (NTS) in an animal model of PONV, to screen a drug candidate and to elucidate the molecular genetic mechanisms of PONV development. Methods Twenty‐one female musk shrews were assigned into three groups: the Surgery group (shrew PONV model, n = 9), the Sham group (n = 6), and the Naïve group (n = 6). In behavioral studies, the main outcome was the number of emetic episodes. In genetic experiments, changes in the transcriptome in the NTS were measured. In a separate study, 12 shrews were used to verify the candidate mechanism underlying PONV. Results A median of six emetic episodes occurred in both the Sham and Surgery groups. Whole‐transcriptome analysis indicated the inhibition of the GABAB receptor‐mediated signaling pathway in the PONV model. Baclofen (GABAB receptor agonist) administration eliminated emetic behaviors in the shrew PONV model. Conclusions Our findings suggest that the GABAB receptor‐mediated signaling pathway is involved in emesis and that baclofen may be a novel therapeutic or prophylactic agent for PONV. Whole‐transcriptome analysis indicated the inhibition of the GABAB receptor‐mediated signaling pathway in the shrew PONV model. After the shrew emetic behaviors, the increase in ADCY1 gene expression, which translates adenyl cyclase (orange), the decrease in GABBR1 gene expression, which translates GABAB receptor R1 subunit (green), and the decrease in CACNB1 gene expression, which translates voltage‐gated calcium channel (blue), were observed. Pharmacological baclofen (GABAB receptor agonist) administration eliminated emetic behaviors in the shrew PONV model.