Contralateral but not systemic administration of bupivacaine reduces acute inflammation in the rat hindpaw.

The effects of contralateral treatment with local anesthetics following acute hindpaw inflammation were investigated in rats. Inflammation was induced by unilateral injection of either 50 or 100 microl of 1% carrageenan into the right paw. Contralateral injection of either bupivacaine or saline was given immediately before the carrageenan. Hindpaw edema and withdrawal responses to thermal and mechanical stimulation were evaluated after 3, 6 and 24h. The results showed that the pro-inflammatory effects of carrageenan were strongest at 6 h after the injection of 100 microl carrageenan with bilaterally decreased withdrawal latencies and ipsilateral edema formation. Contralateral treatment with bupivacaine (1.25, 2.5 or 5 mg/ml) dose-dependently reduced nociceptive behavior for 3-24h. The edema was also reduced at 6h. No effects on pain-related behavior were observed following systemic administration of bupivacaine. Sciatic nerve ligation on the contralateral side or intrathecal administration of saline significantly reduced the effects of bupivacaine when respectively compared with sham-operation and subcutaneous saline injection. Contralateral treatment with bupivacaine into the knee joint induced the same anti-nociceptive effect as administered into the paw. Our findings indicate that contralateral administration of bupivacaine induces long-lasting anti-nociceptive effects and may serve as a new or complementary treatment approach in acute inflammatory pain conditions.