Evaluation of the efficacy of a bioerodible bupivacaine polymer system on antinociception and inflammatory mediator release

Pain due to tissue injury is often characterized by the presence of hyperal gesia and allodynia. It is hypothesized that these perceptual states are me diated by sensitization of peripheral terminals of primary afferent neurons together with several changes in the central nervous system. This provides a rationale for preemptive analgesia, whereby the blockade of primary affe rent input prior to injury may result in a reduction of post-injury pain. O ne approach for prolonged blockade of primary afferent input is the use of bioerodible polymer systems providing regulated release of local anesthetic s. Bioerodible polymer systems offer the theoretical advantage of controlle d drug delivery maintained over prolonged periods. Local application of thi s system to the inflamed tissue compartment permits the use of smaller tota l drug doses. This may minimize systemic side effects, while maintaining pr olonged peripherally-mediated antinociception. In the present study, we eva luated the effects of a bioerodible polymer/bupivacaine system (PLGA/bupiva caine) on several indices of inflammation and on hindpaw levels of the infl ammatory mediators, substance P and bradykinin in the complete Freund's adj uvant model. We observed that PLGA/bupivacaine reduces inflammatory hyperal gesia, edema and hyperthermia in a temporal and dose-related fashion in awa ke animals. Moreover, we demonstrated that PLGA/bupivacaine has a prolonged inhibitory effect on the tissue levels of substance P and bradykinin in th e inflamed hindpaws, The results of these studies clearly indicate the pote ntial therapeutic utility of the PLGA bupivacaine system, with the single d ose administration producing a prolonged suppression of hyperalgesia, edema and biochemical indices of inflammation. (C) 1999 International Associatio n for the Study of Pain. Published by Elsevier Science B.V.