Sub-anesthetic doses of bupivacaine or lidocaine increase peripheral ICS-205 930-induced analgesia against inflammatory pain in rats

Intraplantar co-administration of sub-anesthetic doses of bupivacaine (2.5 μg) or lidocaine (7.5 μg) increased the dose- and time-dependent analgesic effects of the 5-HT 3 receptor antagonist, 3-a-tropanyl-1-H-indole-3-carboxylic ester (ICS-205 930) (1–100 μg; 50 μl) against inflammatory pain induced by hindpaw inoculation with complete Freund's adjuvant. The effects of bupivacaine were greater than lidocaine at all doses of ICS-205 930 tested. These findings may reflect facilitation of ICS-205 930 effects through negative allosteric modulation by bupivacaine and lidocaine of peripheral 5-HT 3 receptors involved in nociceptive processing.