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

Abstract

Purpose: This study was conducted to determine whether hyperalgesic effects of subanaesthetic concentrations of thiopentone could be attributed to GABAA receptor effects. Methods: All studies were performed on 50 rats in a prospective, randomized, blinded fashion using saline-injected animals as controls. Using a modified Randall-Selino 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 iv 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. Results: 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. Conclusion: The results of these studies suggest that hyperalgesia associated with thiopentone is not mediated primarily by GABAA receptors.