The influence of opioid receptor subtypes on the processing of nociceptive inputs in the spinal dorsal horn of the cat.

Extracellular recordings were made of the cutaneous sensory responses of spinocervical tract (SCT) neurones in the lumbar dorsal horn of anaesthetised and paralysed cats. All of the neurones studied were multireceptive, showing excitatory responses to both innocuous and noxious (thermal and when tested, mechanical) stimuli applied to their cutaneous receptive fields on the ipsilateral hindlimb. The effects of iontophoretically applied opioids were studied on a regular cycle of responses to these cutaneous stimuli and also to D.L-homocysteic acid (DLH). In the first series of experiments, drugs were applied in the vicinity of the SCT neurones. The kappa-receptor agonists dynorphin A(1-13) and U50488H, but not dynorphin A(2-13), the mu-agonist DAGO, or the delta-agonist DADL, caused a selective reduction of the nociceptive responses of the neurones. The corresponding responses to innocuous stimuli or to DLH, and spontaneous activity were unaffected. In the second series of experiments, drugs were applied from a second electrode placed in the region of the substantia gelatinosa directly dorsal to the tip of the recording electrode. Under these conditions, the mu-receptor agonist DAGO, but not the kappa-agonist dynorphin A(1-13) or the delta-agonists DADL, DSLET or DLPEN, showed a selective antinociceptive effect. In both series, the antinociceptive effects of the opioids were readily reversed by iontophoretically applied naloxone. The effect of dynorphin A(1-13) applied close to SCT neurones, but not that of DAGO applied in the region of the substantia gelatinosa, was reversed by the alpha 2-adrenoceptor antagonist, idazoxan. The results indicate that both mu- and kappa-opioid receptors (at anatomically distinct sites) can participate in the selective antinociceptive influence that opioids can exert over somatosensory information ascending to supraspinal levels. The antagonism of kappa-receptor-mediated antinociception by idazoxan is consistent with an interaction of opioid and noradrenaline influences at the level of the dorsal horn.