NOCIFENSIVE REFLEX THRESHOLDS IN RATS - MEASURES OF CENTRAL-NERVOUS-SYSTEM EFFECTS OF BARBITURATES

Purpose: To characterize the pharmacodynamic relationships between pla sma pentobarbitone and thiopentone concentrations and nocifensive refl exes during emergence from anaesthesia. Methods: Forty-nine rats were studied, Plasma barbiturate concentrations were measured with high per formance liquid chromatography. Nocifensive reflexes were assessed wit h the hindlimb withdrawal latency (WL) to heat and the somatic motor r esponse threshold (SMRT) to tail pressure. in Protocol I, SMRT; WL, se dation, and the presence of paw-licking and the righting reflex were a ssessed in unrestrained rats before and every 10 min for two hours aft er an intraperitoneal injection of pentobarbitone (30 mg.kg(-1)), Plas ma pentobarbitone kinetics were determined in a separate group of rats . In Protocol II, SMRT and drug concentrations were measured concurren tly in partially restrained animals before and for 35 min after a comp uter-controlled iv bolus of thiopentone, in Protocol III the SMRT-plas ma thiopentone relationship was determined during increasing and decre asing plasma thiopentone concentrations. Results: Enhancement of both nocifensive reflexes was observed in the unrestrained animals. Enhance ment of SMRT was maximal [175% (153-197) of control values] at a mean plasma thiopentone concentration of 11 (9-13) mu g.ml(-1). The SMRT-pl asma thiopentone curve showed a mean efflux-influx difference in plasm a thiopentone concentration of 4 (2.3-5.7) mu g.ml(-1). Conclusion: Ba rbiturate-associated nocifensive reflex enhancement occurs in unrestra ined animals with both thermal and pressure stimuli, The SMRT-plasma t hiopentone concentration relationship during emergence from anaesthesi a was similar to that observed previously during induction, The thiope ntone plasma concentration-SMRT plot showed an equilibration delay sim ilar to that previously described by others for thiopentone at an elec troencephalographic effect site.