Perineural Liraglutide Prolongs Bupivacaine Sciatic Nerve Block and Reduces Inflammation in Rats

Peripheral nerve blocks are crucial for pain management, but their duration is often limited by the local anesthetic's half-life, necessitating adjuvants to extend efficacy and reduce post-block inflammation. Bupivacaine, a common local anesthetic, can cause local tissue inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RA) like liraglutide are known for their neuroprotective and anti-inflammatory properties, making them potential candidates for perineural adjuvants. However, their direct role in modulating peripheral nerve blocks and local tissue response has been largely unexplored, representing a significant gap in current pain management strategies.

Researchers randomized 40 male Wistar rats into five groups to evaluate the effects of perineural liraglutide on bupivacaine-induced sciatic nerve block. Group I received perineural 0.5% bupivacaine alone. Groups II and III received perineural 0.5% bupivacaine combined with liraglutide (at 1.8 mg/kg or 3.6 mg/kg, respectively). Group IV received perineural 3.6 mg/kg liraglutide alone. Group V received perineural 0.5% bupivacaine concurrently with systemic 3.6 mg/kg liraglutide (intraperitoneal). Sciatic nerve blocks were performed under nerve stimulation, and sensory, motor, and proprioceptive functions were assessed every 10 min until complete recovery. At 24 h, sciatic nerves were harvested for blinded histopathological evaluation.

High-dose perineural liraglutide significantly prolonged the duration of bupivacaine-induced sciatic nerve block compared to bupivacaine alone. Sensory block duration increased from 120 min (interquartile range [IQR] 107.5-130) to 170 min (IQR 160-180) with high-dose perineural liraglutide (p=0.009). Motor block duration similarly extended from 115 min (IQR 100-120) to 160 min (IQR 160-170) (p=0.007). Proprioceptive block duration also saw a significant increase from 115 min (IQR 100-122.5) to 170 min (IQR 167.5-170) (p=0.009). Systemic liraglutide did not replicate these effects, indicating a local mechanism. Histopathological analysis revealed a significant reduction in perineural inflammation in all liraglutide-treated groups (p<0.001), with no evidence of myelin damage at 24 h. This suggests liraglutide acts as a safe, local anti-inflammatory and block-prolonging agent.

The high-dose perineural liraglutide group experienced a 41.7% increase in sensory block duration and a 39.1% increase in motor block duration compared to bupivacaine alone.