The actions of 5-HT₁ agonists and antagonists on nociceptive processing in the rat spinal cord: results from behavioural and electrophysiological studies

We have developed a technique which allows drugs to be microinjected intrathecally in anaesthetized rats whilst single unit recordings are made from dorsal horn neurones. Using this technique together with recordings of tail flick latency (TFL) elicited from lightly anaesthetized rats we have found that the specific 5-HT_1a agonist 8-OH DPAT (15, 150, 300 nmol) increases nociceptive responses recorded from single dorsal horn neurones and decreases TFL. The non-specific 5-HT_1b agonist TFMPP (300 nmol) and the general 5-HT₁ agonist 5-CT (0.3, 3.0, 30 nmol) both decreased nociceptive responses and has inconsistent effects on TFL. Intrathecally applied 5-HT (130, 260 nmol) generally reduced nociceptive neuronal responses and increased TFL. In a minority of experiments, however, 5-HT increased nociceptive responses and it is suggested that this effect is associated with activation of 5-HT_1a receptors. Activity at 5-HT_1b receptors has the effect of suppressing or reducing responsiveness. The increased responsiveness of dorsal horn neurones to noxious stimulation associated with activity at 5-HT_1a receptors may be associated either with increases in receptive field size, promotion of spinal nocifensive reflexes or the facilitation of the rostral transmission to specific brainstem sites.