PREEMPTIVE ANALGESIC EFFECTS OF STEROID ANESTHESIA WITH ALPHAXALONE IN THE RAT FORMALIN TEST - EVIDENCE FOR DIFFERENTIAL GABA(A) RECEPTOR MODULATION IN PERSISTENT NOCICEPTION

Background: The role of preemptive treatment with volatile and intrave nous anesthetics has been examined in previous studies using the rat f ormalin test. Evidence describing analgesic properties of the gamma-am ino butyric acid-ergic (GABAergic) steroid anesthetics, such as alphax alone, suggest that they may suppress the development of central sensi tization to pain. This study examined the preemptive effects of alphax alone in comparison with other GABAergic anesthetics, propofol and pen tobarbital. Methods: The pain behavior of rats was evaluated (using th e previously validated weighted scores method of behavioral rating) 15 -60 min after subcutaneous hind paw injection of 50 mu l 1.5% formalin . In each trial, anesthetics and their respective vehicles were admini stered by tall-rein injection either 0.5-10 min before or 5 min after, formalin injection. When analgesic effects were observed with any of these agents, further studies were conducted with a GABA(A) receptor a ntagonist in an attempt to confirm a specific receptor-mediated action of the agent. Results: Alphaxalone pretreatment produced transient an algesia in the early part of phase 2, which was not observed in rats p osttreated with alphaxalone. The analgesic effect of alphaxalone was a ntagonized by picrotoxin, as well. Neither pentobarbital nor propofol showed any analgesic effects at the doses used in our study. Conclusio ns: Whereas alphaxalone was shown to produce preemptive analgesia thro ugh its action at the GABA(A) receptor, pentobarbital and propofol, wh ich also are known to act at this site, showed no analgesic effects. T he diversity of receptor subtypes and functional complexity of GABA(A) receptors is such that steroid anesthetics may have effects that are different from other GABAergic agents. Further research into the role of progesterone metabolites and steroid anesthetics in the prevention of central sensitization may hare clinical implications for the treatm ent of acute or chronic pain.