Role of different 5-HT receptor subtypes in modulating nociception in the rat

Several lines of evidence have implicated a role for the descending serotonergic system in the modulation of somatosensory transmission and in analgesia. It is now known that serotonin (5-HT) has more than one type of receptor. The aim of the present experiments was to investigate the involvement of different 5-HT receptor sites in antinociception and analgesia. By employing agonists and antagonists selective for different types of 5-HT receptors in ionophoretic experiments, it was shown that 5-HT^ and not 5-HT2 receptors were responsible for mediating the heterogeneous effects of ionophoretically applied 5-HT on rat dorsal horn neurones. Two different 5-HT-j receptor subtypes were found to mediate qualitatively different effects, often on the same cell. Whereas the 5-HT^g site appeared to mediate the selective antinociceptive effect of 5-HT, non-selective effects of ionophoretically applied 5-HT, appeared to be exerted through the 5-HT^ receptor site. Focal brainstem stimulation experiments have demonstrated that both the selective antinociceptive and non-selective inhibitory effects of stimulation in the medullary serotonergic nucleus raphe magnus on dorsal horn neurones are mediated through a 5-HT^-type receptor. Thus a 5-HT-| and not a 5-HT2 receptor antagonist could readily reverse the effects of brainstem stimulation. A pilot behavioural study investigated the analgesic potential of two different 5-HT-| receptor subtype agonists and preliminary evidence appears to confirm the involvement of the 5-HT-|g receptor type in behavioural analgesia. The findings of the present study are discussed in relation to previous reports in the literature