5-Hydroxytryptamine-induced sensitization and activation of peripheral fibres in the neonatal rat are mediated via different 5-hydroxytryptamine-receptors.

The effects of 5-hydroxytryptamine on peripheral nociceptive fibres were studied in an in vitro preparation of the neonatal rat spinal cord with attached tail. The activation of peripheral fibres in the tail by noxious stimuli (bradykinin, capsaicin, heat) was recorded as a depolarization of a ventral root in the lumbar region of the spinal cord (L3-L5). Responses evoked by brief applications of submaximal or threshold concentrations of bradykinin or capsaicin to the tail were enhanced by 5-hydroxytryptamine and the 5-hydroxytryptamine1C/5-hydroxytryptamine2-receptor agonist alpha-methyl-5-hydroxtryptamine but not by the 5-hydroxytryptamine3-receptor agonist 2-methyl-5-hydroxytryptamine or the 5-hydroxytryptamine1-receptor agonist 5-carboxamidotryptamine. Sensitization induced by 5-hydroxytryptamine and alpha-methyl-5-hydroxytryptamine was blocked by the selective 5-hydroxytryptamine2-receptor antagonist ketanserin. Neither the 5-hydroxytryptamine3/5-hydroxytryptamine4-receptor antagonist ICS 205-930 nor the 5-hydroxytryptamine1/5-hydroxytryptamine2-receptor antagonist methiothepin blocked the 5-hydroxytryptamine-induced sensitization. The responses evoked by submaximal thermal stimuli were also enhanced following the sensitization of peripheral nociceptors with 5-hydroxytryptamine or alpha-methyl-5-hydroxytryptamine. The alpha-methyl-5-hydroxytryptamine-induced enhancement of thermal responses was reduced by ketanserin. 5-Hydroxytryptamine did not evoke a ventral root response unless peripheral fibres were sensitized with threshold concentrations of bradykinin or capsaicin. This effect was mimicked under the same conditions by 5-carboxamidotryptamine but not by alpha-methyl-5-hydroxytryptamine or 2-methyl-5-hydroxytryptamine. The excitatory effect of 5-hydroxytryptamine was blocked by methiothepin but not by ICS 205-930 or ketanserin. Neither 5-hydroxytryptamine-induced sensitization nor 5-hydroxytryptamine-evoked activation of peripheral fibres was blocked by indomethacin. These data indicate that two types of receptor are involved in the peripheral actions of 5-hydroxytryptamine in nociception. 5-Hydroxytryptamine-induced sensitization involves a 5-hydroxytryptamine2-receptor, whereas 5-hydroxytryptamine-evoked excitation involves a 5-hydroxytryptamine1-like-receptor.