Antinociceptive actions of descending catecholaminergic tracts on dorsal horn somatosensory neurones

Abstract

Ionophoretically-applied dopamine and noradrenaline selectively inhibited the nociceptive responses of multireceptive somatosensory dorsal horn neurones, whilst non-nociceptive responses, spontaneous activity and activity evoked by an ionophoretically-applied excitatory amino acid, DL-homocysteic acid were unaffected. Many of the neurones tested had long ascending projections, capable of transmitting nociceptive information to supraspinal sites; in the rat (spinothalamic tract neurones) and in the cat (spinocervical tract neurones).The use of ionophoretically-applied receptor-specific agonists and antagonists demonstrated that the actions of noradrenaline and dopamine were pharmacologically distinct. The selective antinociceptive action produced by noradrenaline was mediated by an 06,-adrenoreceptor, whilst the selective antinociceptive effect of dopamine was mediated by a dopamine receptor.A glyoxylic-acid histofluorescence study was undertaken to ascertain the optimal stereotaxic placement of stimulating electrodes, in the regions of those dopamine cell groups (A9 and All) that have been considered to provide a spinal projection.Focal electrical stimulation in the region of the All dopamine cell group evoked a selective antinociceptive effect on multireceptive dorsal horn neurones in the rat. This stimulus-evoked effect was rapidly and consistently reversed by ionophoresis of the D₂ dopamine-receptor antagonist, sulpiride, in the vicinity of the dorsal horn neurone being tested, whilst an opiate antagonist (naloxone) and an α₂-antagonist (RX781094) had no effect. Using the same parameters, focal electrical stimulation in the region of the A9 dopamine cell group did not affect the evoked responses of any multireceptive neurones tested.The results of this study present data supporting selective antinociceptive roles for dopamine and noradrenaline at the spinal level. The All dopamine cell group was demonstrated as a supraspinal source of a selective antinociceptive effect, mediated by dopamine at the level of the dorsal horn.