An α 2 receptor mediates the selective inhibition by noradrenaline of nociceptive responses of identified dorsal horn neurones

Abstract

Extracellular recordings were made of 59 neurones with long, ascenfing projections (spinocervical tract (SCT) and dorsal column postsynaptic (DCPS) neurones) in the lumbar dorsal horn of anaesthetized and paralyzed cats. All showed prominent excitatory responses to innocuous stimuli, applied to their cutaneous receptive fields on the ipsilateral hindlimb. The majority of the population investigated (83%) was multireceptive, being activated by noxious as well as innocuous cutaneous stimuli. Drug effects were examined on a regular cycle of responses to these cutaneous stimuli and also to dl-homocysteic acid (DLH). In 49 multireceptive SCT and DCPS neurones, ionophoretically-applied l-noradrenaline (NA) produced a potent selective inhibition of the nociceptive responses (to heat or pinch) in 40 out of 44 SCT and 3 out of 5 DCPS neurones, with no statistically significant change in the responses to innocuous brush or DLH, or in spontaneous activity. NA had no effect on the majority of cells (8 out of 11) that responded only to innocuous stimuli. In 19 SCT neurones that showed NA-selectivity, the α 2-selective agonists clonidine (in 12 out of 15) and metaraminol (in 2 out of3) mimicked this selective effect, whereas, the α 1 agonist, phenylephrine and the β agonist, isoprenaline did not. Furthermore, the α antagonists, yohimbine and idazoxan (RX781094), either reversed or reduced the potency of the NA-elicited inhibition of nociceptive responses in all SCT neurones tested. These results are discussed in relation to other evidence for spinal antinociceptive effects of noradrenergic systems acting at a spinal level and the possible involvement of an α 2 receptor in such effects.