Liposomal Bupivacaine: A Delay Rather Than Elimination of Rebound Pain in Mouse Postoperative Model

Background: Rebound pain, a postoperative surge in pain after peripheral nerve block (PNB) resolution, leads to increased opioid use and delayed recovery. Liposomal bupivacaine (LB) resolution prolongs analgesia, but its impact on rebound pain remains unclear. We developed a mouse model of sciatic/femoral nerve block to study LB’s effects. Methods: Male C57 mice (n=24) underwent tibial fracture surgery and were divided into sham, surgery (S), or LB (1.3%) groups. LB was administered near sciatic/femoral nerves using nerve stimulator guidance. Mechanical (von Frey) and thermal (Hargreaves) nociception were assessed. Histology evaluated nerve inflammation at days 2 and 28. Nerve block success rates were confirmed via methylene blue injection (n=15). Results: LB extended thermal (24h, P <0.05) and mechanical (36h, P <0.05) analgesia. Transient thermal rebound hyperalgesia occurred at 48h ( P =0.003), but no mechanical rebound was observed. Mild neural inflammation was more frequent with LB at day 2 ( P <0.05). Nerve stimulator-guided blocks had high success rates (sciatic: 93.3%, P =0.035; femoral: 73.3%, P =0.030). Conclusions: LB delayed but did not eliminate rebound pain, possibly due to neuroinflammation. A reliable mouse model of combined sciatic/femoral nerve block was established.