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ANESTHETIC PHARMACOLOGY

Tumor Necrosis Factor- Reduces Ketamine- and Propofol-Induced Anesthesia Time in Rats

Department of Anesthesiology, University of Hirosaki School of Medicine, Japan

Address correspondence and reprint requests to T. Yasuda, MD, Department of Anesthesiology, University of Hirosaki School of Medicine, 5 Zaifu-Cho, Hirosaki 036-8216, Japan. Address e-mail to masuika{at}cc.hirosaki-u.ac.jp

Tumor necrosis factor- (TNF) is a crucial neuromodulator in the brain. TNF is involved in many physiological events including pain response and sleep. However, the interactions between TNF and anesthetics have not been elucidated yet. In the present study, we investigated the effects of four intracerebroventricular (ICV) doses (1, 10, and 100 pg, and 1 ng) and two intraperitoneal (IP) doses (10 and 100 ng) of TNF on anesthesia time of ketamine (100 mg/kg IP) and propofol (80 mg/kg IP) in rats. All ICV doses of TNF reduced anesthesia time of ketamine and propofol compared with the saline ICV group (ketamine control group, 45.4 ± 6.5 min; propofol control group, 43.5 ± 11.0 min). The maximum effect was obtained after the ICV injection of 10 pg of TNF (76% and 54% of ketamine and propofol control groups, respectively). Anesthesia time of ketamine or propofol was also decreased by IP injection of TNF in a dose-dependent manner. Injection of 100 ng of TNF IP reduced anesthesia time of ketamine and propofol by 67% and 64% of each control group, respectively. These data show that TNF can modulate the anesthesia time of IV anesthetics, suggesting that anesthetic requirements might be altered in the presence of cerebral or systemic inflammation.

IMPLICATIONS: Tumor necrosis factor alpha (TNF) regulates many physiological events in the brain. We investigated the effects of TNF on anesthesia time in rats. Both central and peripheral administration of TNF decreased anesthesia time induced by ketamine and propofol.

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