Perineural dexamethasone attenuates liposomal bupivacaine-induced delayed neural inflammation in mice in vivo

Background: Liposomal bupivacaine (Exparel (R)) is a sustained-release formulation of bupivacaine for use in surgical infiltration anaesthesia. We analysed the histological nerve toxicity and clinical effectiveness of perineural Exparel (R) alone or with added dexamethasone in a mouse model. Methods: We assigned 98 mice receiving a perineural sciatic nerve injection into seven groups: sham (n=14, perineural saline), B (n=14, perineural bupivacaine), BDIP (n=14, perineural bupivacaine thorn intraperitoneal dexamethasone), BDPN (n=14, perineural bupivacaine thorn perineural dexamethasone), E (n=14, perineural Exparel (R)), EDIP (n=14, perineural Exparel (R) thorn intraperitoneal dexamethasone), and EDPN (n=14, perineural Exparel (R) thorn perineural dexamethasone). The duration of thermoalgesic and motor block was evaluated in 49 mice (seven mice randomly selected by group) every 30 min until recovery. Mice were killed for sciatic nerve histological assessment at 14 or 28 days. Results: The median duration of motor block was 90, 120, 120, 120, 180, and 180 min and the duration of thermoalgesic block was 240, 300, 360, 360, 360, and 420 min for groups B, BDIP, BDPN, E, EDIP, and EDPN, respectively. The B group mice showed mild neural inflammation at 14 days and the E group mice showed mild neural inflammation at 28 days. Addition (intraperitoneal or perineural) of dexamethasone reduced neural inflammation induced by bupivacaine, whereas only perineural dexamethasone reduced neural inflammation induced by Exparel (R). Conclusions: Perineural or systemic dexamethasone had a protective effect against the neural inflammation induced by bupivacaine, and perineural dexamethasone attenuated delayed inflammation induced by perineural Exparel