ABSTRACT
Involvements of kinin and prostaglandin and their interaction in noxious thermal stimuli were investigated in noninflamed and inflamed rats. The nociceptive response was evaluated from the escape latency of foot withdrawal to the thermal stimuli with a beam of light. The escape latency in kininogens-deficient Brown Norway (B/N-) Katholiek rats was significantly longer than that in the normal strain, B/N-Kitasato rats. The latency in B/N-Kitasato rat was prolonged by administration of a bradykinin (BK) B2 receptor antagonist, FR173657 (30 mg/kg, p.o.), whereas it was shortened by pretreatment with a kininase II inhibitor, captopril (10 mg/kg, i.p.). Both agents did not affect the latency in B/N-Katholiek rats. In normal Sprague-Dawley (SD) rat, administration of indomethacin did not change the escape latency against the thermal stimuli. In contrast, administration of indomethacin or a relatively cyclooxygenase-1-selective inhibitor, mofezolac (10 mg/kg, p.o.) significantly reduced numbers of writhing reaction in mice induced by acetic acid solution. Injection of lipopolysaccharide (1 mg/kg, i.v.) resulted in shortening escape latency at 8 h after the injection in B/N-Kitasato rats. This hyperalgesia could be reversed by pretreatment of the rats with indomethacin, a cyclooxygenase-2-selective inhibitor JTE-522 (10 mg/kg, p.o.), or FR173657, but not with mofezolac. The hyperalgesia was not seen in B/N-Katholiek rats. These results indicate that kinin has major participation in peripheral skin thermal nociception under noninflamed condition, although cyclooxygenases may have little participation. Prostaglandins produced by cyclooxygenase-2 could coordinate with BK to elicit hyperalgesia during inflammation induced by lipopolysaccharide.
Subject(s)
Behavior, Animal/drug effects , Bradykinin Receptor Antagonists , Hyperalgesia/metabolism , Prostaglandins/biosynthesis , Animals , Behavior, Animal/physiology , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Escape Reaction/drug effects , Escape Reaction/physiology , Hot Temperature , Hyperalgesia/drug therapy , Hyperalgesia/physiopathology , Isoenzymes/antagonists & inhibitors , Kininogens/deficiency , Lipopolysaccharides/pharmacology , Male , Membrane Proteins , Mice , Mice, Inbred ICR , Pain Measurement , Prostaglandin-Endoperoxide Synthases , Rats , Rats, Inbred BN , Rats, Sprague-Dawley , Receptor, Bradykinin B2 , Receptors, Bradykinin/biosynthesis , Species SpecificityABSTRACT
The purpose of this study is to examine changes in serum and urinary inorganic fluoride (F) concentrations with their effects on renal and hepatic functions after repeated sevoflurane anesthesia with relatively short time interval. Eight patients received sevoflurane anesthesia twice within 7 days for gynecological surgery. Serum and urine F levels before induction, 0.5 and 1 hour after induction, and 0.5 hour after anesthesia were compared between first and second anesthesia. There were no significant differences in serum and urine F concentrations at the same point between first and second anesthesia. Two obese patients exhibited peak concentrations greater than 50 mumol.l-1 of F. Laboratory findings of renal function remained stable throughout 2 operations, whereas hepatic function deteriorated in the two obese patients after the first anesthesia, and resolved within 14 days after the second anesthesia. In conclusion, it is suggested that the second exposure to sevoflurane within 7 day interval does not alter the sevoflurane metabolism. However, obesity may contribute to a rise in serum inorganic fluoride after repeated sevoflurane anesthesia.
