THIOPENTONE INDUCED ENHANCEMENT OF SOMATIC MOTOR-RESPONSES TO NOXIOUS-STIMULATION - INFLUENCE OF GABA(A) RECEPTOR MODULATION

Purpose: This study was;conducted to determine whether hyperalgesic ef fects of subanaesthetic concentrations of thiopentone could be attribu ted to GABA(A) receptor effects. Methods: All studies were performed o n 50 rats in a prospective, randomized, blinded fashion using saline-i njected animals as controls. Using a modified Randall-Selitto techniqu e, the motor behavior stimulated by noxious stimulation was quantified by determining the lowest tail pressure required to provoke a withdra wal response (somatic motor response threshold, SMRT). In the first pr otocol (21 rats), we studied the effects of 0.5, 1.5 and 5 mg . kg(-1) iv of the GABA(A) 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 GABA, antagonist, bicuculline 0.25 mg . kg( -1) upon the SMRT-reducing effects of a standardized thiopentone infus ion 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 wit h muscimol (0.5 mg . kg(-1)), thiopentone produced analgesia, as shown by an increase in SMRT (P = 0.009). In the bicuculline treated animal s, SMRT decreased linearly with increasing plasma thiopentone concentr ations (P < 0.001). The slope of the relationship in the bicuculine gr oup was not significantly different from that observed in the saline-t reated group, indicating that bicuculline did not block the hyperalges ic effects of thiopentone. Conclusion: The results of these studies su ggest that hyperalgesia associated with thiopentone is not mediated pr imarily by GABA(A) receptors.