Glucocorticoids prolong rat sciatic nerve blockade in vivo from bupivacaine microspheres

Background: previous work showed that incorporation of dexamethasone (0.05 weight/weight percentage) into bupivacaine microspheres prolonged blockade by eight to 13 times compared with that produced by bupivacaine microspheres alone. The determinants of dexamethasone's block-prolonging effect were examined and reported here. Methods: Polylactic-co-glycolic acid polymer microspheres (65/35) with 75 weight/weight percentage bupivacaine were prepared. Microspheres were injected adjacent to the rat sciatic nerve, and sensory and motor blockade were assessed. A procedure was developed to test drugs for block-prolonging ability in vivo by placing test drugs in the injection fluid along with a suspension of bupivacaine microspheres. Results: Dexamethasone alone in suspension did not produce blockade, nor did it prolong blockade induced by aqueous bupivacaine. Bupivacaine microspheres (150 mg drug/kg rat weight) produced blockade for 6 to 10 h. Dexamethasone in the suspending solution of microspheres prolonged block by up to five times. Glucocorticoids prolonged block in proportion to glucocorticoid/antiinflammatory potency. The corticosteroid antagonist cortexolone inhibited dexamethasone's blockade-prolonging action. Durations of blockade with or without dexamethasone were unaltered by hydroxyurea-induced neutrophil depletion. Microspheres were extracted from rats at time points ranging from 7 h to 7 days, and residual microsphere dry weight and bupivacaine content were similar in groups of rats injected with either bupivacaine microspheres or bupivacaine microspheres containing dexamethasone, respectively. Conclusions: Glucocorticoids prolong blockade from bupivacaine microspheres. The mechanism appears unrelated to the kinetics of bupivacaine release in vivo.