Antinociceptive effect of ketanserin in mice: involvement of supraspinal 5-HT2 receptors in nociceptive transmission.

The involvement of 5-HT2 receptors in pain transmission was investigated in mice. Subcutaneous administration of the selective 5-HT2 receptor antagonist ketanserin produced dose-dependent antinociception in the hot-plate and acetic acid-induced writhing tests with ED50 values (95% confidence limit) of 1.51 (1.13-1.89) and 0.62 (0.10-1.40) mg/kg, respectively, but was without any significant effect on the tail-flick test. Pretreatment with the catecholamine depletors 6-hydroxydopamine (2.5 micrograms, i.c.v.) or alpha-methyl-p-tyrosine (200 mg/kg, s.c.), or the serotonin synthesis inhibitor p-chlorophenylalanine methylester (200 mg/kg, s.c.), resulted in a significant decrease in the antinociceptive effect of ketanserin. Likewise, intrathecal (i.t.) administration of 1 microgram/mouse of idazoxan (an alpha 2-antagonist), methysergide (mixed 5-HT1, and 5-HT2 antagonist) or ketanserin also reversed the antinociceptive effect of s.c. administered ketanserin. The results of this work indicate that 5-HT2 receptors located supraspinally may inhibit descending nociceptive neurotransmission. In addition, these studies suggest that 5-HT2 receptors located at the spinal level modulate nociception.