Analgesia with anesthetic steroids and ethanol

Ethanol is well known to enhance the potencies of a range of anesthetics. However, its effects on steroid anesthesia have not been reported. Because ethanol often is added to the delivery vehicle to increase steroid solubility, it is important to evaluate its contribution to steroid anesthesia. Intravenous injection of ethanol and anesthetic steroid(s) produced marked analgesia and a marked increase in the number of mice exhibiting the loss of righting response (LRR). Ethanol alone at these low doses was merely sedative, and steroid alone was hypnotic without any analgesic benefit. The nocifensive response to tail clamp was used as a measure of analgesia. Progesterone or the anesthetic steroid, 3 alpha-hydroxy-5 alpha- pregnan-20-one (3 alpha) alone reduced, but did not abolish the nocifensive response. Progesterone (80 mg/kg) or 3 alpha (3 mg/kg) administered together with ethanol (1.1 g/kg) abolished the nocifensive response (analgesia) and resulted in LRR within 10 s. The onset of both effects was rapid, and the duration was greater than 8 min. With 3 alpha alone, the reduced nocifensive behavior fully returned before the mouse regained the righting response. Thus, the evaluation of the nocifensive response is not precluded by LRR. The rapid onset of LRR and analgesia suggest that 3 alpha and progesterone, not their metabolites, are responsible for the observed activities.