Tumor necrosis factor-alpha reduces ketamine- and propofol-induced anesthesia time in rats.
Tumor necrosis factor-alpha (TNFalpha) is a crucial neuromodulator in the brain. TNFalpha is involved in many physiological events including pain response and sleep. However, the interactions between TNFalpha 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 TNFalpha on anesthesia time of ketamine (100 mg/kg IP) and propofol (80 mg/kg IP) in rats. All ICV doses of TNFalpha 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 TNFalpha (76% and 54% of ketamine and propofol control groups, respectively). Anesthesia time of ketamine or propofol was also decreased by IP injection of TNFalpha in a dose-dependent manner. Injection of 100 ng of TNFalpha IP reduced anesthesia time of ketamine and propofol by 67% and 64% of each control group, respectively. These data show that TNFalpha can modulate the anesthesia time of IV anesthetics, suggesting that anesthetic requirements might be altered in the presence of cerebral or systemic inflammation.


CONCLUSIONS
Tumor necrosis factor alpha (TNFalpha) regulates many physiological events in the brain. We investigated the effects of TNFalpha on anesthesia time in rats. Both central and peripheral administration of TNFalpha decreased anesthesia time induced by ketamine and propofol.
D000778:Anesthetics, Dissociative / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007649:Ketamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D015742:Propofol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine; D015742:Propofol