Thiopentone induced enhancement of somatic motor responses to noxious stimulation: influence of GABAA receptor modulation

Abstract

This study was conducted to determine whether hyperalgesic effects of subanaesthetic concentrations of thiopentone could be attributed to GABAA receptor effects. All studies were performed on 50 rats in a prospective, randomized, blinded fashion using saline-injected animals as controls. Using a modified Randall-Selitto technique, the motor behavior stimulated by noxious stimulation was quantified by determining the lowest tail pressure required to provoke a withdrawal response (somatic motor response threshold, SMRT). In the first protocol (21 rats), we studied the effects of 0.5, 1.5 and 5 mg.kg-1 i.v. of the GABAA agonist, muscimol, on SMRT. In the second protocol (20 rats), the effects of administration of saline, muscimol 0.5 mg.kg-1, or the competitive GABAA antagonist, bicuculline 0.25 mg.kg-1, upon the SMRT-reducing effects of a standardized thiopentone infusion were observed. No dose of muscimol produced hyperalgesia. The highest dose of muscimol used (5 mg.kg-1) produced pronounced analgesic effects, raising the SMRT above 750 g. No change in SMRT was detected with the smaller doses of muscimol. Given in combination with muscimol (0.5 mg.kg-1), thiopentone produced analgesia, as shown by an increase in SMRT (P = 0.009). In the bicuculline treated animals, SMRT decreased linearly with increasing plasma thiopentone concentrations (P < 0.001). The slope of the relationship in the bicuculine group was not significantly different from that observed in the saline-treated group, indicating that bicuculline did not block the hyperalgesic effects of thiopentone. The results of these studies suggest that hyperalgesia associated with thiopentone is not mediated primarily by GABAA receptors.