Effects of the GLP-1 receptor agonist liraglutide on bupivacaine-induced sciatic nerve block in a rat model

Purpose: Glucagon-like peptide-1 receptor agonists exhibit neuroprotective and anti-inflammatory effects; however, their role as perineural adjuvants in peripheral nerve blocks has not been investigated. We evaluated whether perineural liraglutide prolongs bupivacaine-induced sciatic nerve block and attenuates local tissue inflammation in a rat model. Methods: Forty male Wistar rats were randomized into five groups. Group I received perineural bupivacaine alone (0.3 ml 0.5% bupivacaine + 0.2 ml saline). Groups II and III received perineural bupivacaine (0.3 ml 0.5%) combined with liraglutide (0.2 ml; 1.8 or 3.6 mg/kg, respectively). Group IV received perineural liraglutide alone (0.5 ml, 3.6 mg/kg). Group V received perineural bupivacaine (0.3 ml 0.5% + 0.2 ml saline) and concurrently systemic liraglutide (3.6 mg/kg, intraperitoneal). Sciatic nerve block was performed under nerve stimulation. Sensory, motor, and proprioceptive functions were assessed every 10 min until complete recovery. At 24 h, sciatic nerves were harvested for blinded histopathological evaluation. Results: High-dose perineural liraglutide prolonged bupivacaine-induced block duration compared with bupivacaine alone (sensory: 170 [160–180] vs 120 [107.5–130] min, p = 0.009; motor: 160 [160–170] vs 115 [100–120] min, p = 0.007; proprioceptive: 170 [167.5–170] vs 115 [100–122.5] min, p = 0.009). Systemic liraglutide did not reproduce this effect. Histopathologically, perineural inflammation was reduced in liraglutide-treated groups (p < 0.001), with no evidence of myelin damage at 24 h. Conclusion: Perineural liraglutide produces dose-dependent prolongation of bupivacaine sciatic nerve block and reduces perineural inflammation without myelin toxicity. These findings provide proof-of-concept for liraglutide as a novel perineural adjuvant, warranting extended neurotoxicity and further translational studies.