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.
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.