This study was performed to compare the analgesic effects of the systemic versus local administration of ketamine and observe the effects of an NMDA receptor agonist on its peripheral analgesia using the rat formalin test.

Rats undergoing peripheral analgesia were divided into three groups; the administration of a subcutaneous (s.c.) injection of 0.1 ml of normal saline (Control), and intraperitoneal (i.p.) (Keta/IP) and s.c. (Keta/LO) injections of 2.5 mg/0.1 ml of ketamine administered 5 min before a s.c. injection of 50 ul of 5% formalin. All s.c. injections were performed at the same site: the right hind paw of the rat. To observe the effects of an NMDA receptor agonist, five groups were compared. In addition to the control and Keta/LO groups described above, following three groups with 1-Aminocyclopropanecarboxylic acid (ACPC), an NMDA receptor agonist, in addition to the Keta/LO group; local infiltration with 0.1 mM/0.1 ml ACPC 10 min before or after the administration of ketamine, and an i.p. injection 10 min before the administration of ketamine followed by a s.c. injection of formalin 5 min later. The pain behavior was compared according to the number of flinches during phase 2.

All the ketamine groups showed fewer flinches compared to the control (P < 0.01). The Keta/Lo group showed fewer flinches than that of the Keta/IP group (P < 0.01). The analgesic effect of locally administered ketamine was reversed by pretreatment with either s.c. or i.p. ACPC, but not by post-treatment.

These data suggest that locally administered ketamine has a potent peripheral analgesic effect, but the administration of ACPC prior to ketamine decreases the analgesic effect of ketamine.