Systemic administration of magnesium sulfate enhances lidocaine-induced sciatic nerve block and exerts analgesic effects in postsurgical pain in rats

Magnesium plays a role in various physiological processes and has been used for treatment and prevention of diseases affecting different organ systems. Magnesium sulfate has been proposed as an adjuvant for anesthesia, but its efficacy remains debated due to conflicting findings. The present study explored the analgesic effects of different routines of magnesium sulfate administration under three common perioperative situations in rats. The study tested several doses of magnesium sulfate (e.g., 30 mg/kg, 50 mg/kg) in rats under different perioperative conditions: (1) perineural co-administration of magnesium sulfate with lidocaine, (2) intraperitoneally magnesium sulfate pre-administration before lidocaine nerve block, and (3) systemic magnesium sulfate given before or after plantar incision surgery. Sensory/motor blockade duration and mechanical pain thresholds were assessed. When magnesium sulfate is used as an adjunct to lidocaine, all doses of magnesium sulfate can reduce the sciatic nerve block caused by lidocaine. However, when administered via intraperitoneal injection, lower concentrations of magnesium sulfate (e.g., 30 mg/kg, 50 mg/kg) enhance the blocking effect of lidocaine, while higher concentrations (e.g., 150 mg/kg, 300 mg/kg) show no significant additional benefit. In a rat plantar incision model, both preoperative and postoperative intraperitoneal administration of magnesium sulfate effectively alleviated postoperative pain, with the 150 mg/kg dose yielding the most pronounced effect. Magnesium sulfate exhibits route-dependent effects: while it attenuates lidocaine-induced nerve blockade when administered locally, it enhances blockade duration and provides significant analgesia when given systemically. These findings implies that magnesium sulfate paves the way for designing safer nerve block protocols when administered locally, while its systemic application translates into more prolonged and superior postoperative analgesia, thereby reducing opioid consumption and facilitating patient recovery.