Involvement of serotonin mechanisms in the antinociceptive effect of S(+)‐ketoprofen

Serotonin (5‐hydroxytryptamine; 5‐HT) plays a role in the modulation and processing of pain and evidence has been provided that some nonsteroidal anti‐inflammatory drugs (NSAIDs) act, at least in part, through this system. The present study was designed to investigate the possible participation of 5‐HT1, 5‐HT2, 5‐HT3, and 5‐HT7 receptor subtypes in the antinociceptive effect of S(+)‐ketoprofen (S‐KP) at spinal and supraspinal level using the “pain induced functional impairment model in rat” (PIFIR model). S‐KP was administered orally (p.o.) and antagonist drugs for 5‐HT receptors (5‐HT1/5‐HT2, and 5‐HT3) were administered intrathecally (i.t.) or intracerebroventricularly (i.c.v.) 15 min before S‐KP. S‐KP (3.4 mg/kg p.o.) produced a significant antinociceptive effect in this model. Pre‐treatment with the 5‐HT1/5‐HT2/5‐HT7 receptor antagonist, methiothepin (1.5 μg, i.c.v.), significantly reversed the antinociceptive effect of S‐KP. In contrast, no significant differences were observed following i.t. administration of methiothepin. Pre‐treatment i.t., but not i.c.v., with the 5‐HT3/5‐HT4 receptor antagonist, tropisetron (0.9 μg), on the other hand, significantly reversed S‐KP‐induced antinociception. These results indicate that serotonin mechanisms are involved in the antinociceptive effect of S‐KP. 5‐HT1/5‐HT2/5‐HT7 receptors participate at the supraspinal level and 5‐HT3/5‐HT4 receptors participate at spinal level. Drug Dev. Res. 57:187–192, 2002.