Antinociceptive actions of descending dopaminergic tracts on cat and rat dorsal horn somatosensory neurones.
1. The actions of dopamine (DA) and DA receptor specific agonists and antagonist ionophoretically applied in the spinal dorsal horn, and of focal electrical stimulation in the region of the supraspinal DA cell groups (A9 and A11) were assessed on the somatosensory responses of dorsal horn neurones, in both the rat and cat. The neurones tested were multireceptive, giving reproducible responses to both noxious (using a mechanical pinch or radiant heat) and innocuous (using a motorized brush) cutaneous stimuli, as well as to ionophoretically applied DL-homocysteic acid (DLH, a direct excitant). In the cat, all neurones tested were identified as belonging to the spinocervical tract (SCT) and were located in the dorsal horn laminae III-V, whilst in the rat, spinothalamic tract (STT) and spinomesencephalic (SMT) neurones located in the region of lamina I and laminae III-V were tested. 2. Ionophoretically applied DA and RU24213, a D2 DA receptor agonist, caused a selective inhibition of the responses to noxious stimuli of SCT, STT and SMT neurones, whilst the responses to non-nociceptive stimuli, spontaneous activity and DLH-evoked activity were unaffected. This action was reversed in the presence of sulpiride, the highly selective D2 DA receptor antagonist. Neither sulpiride alone nor SKF38393, a D1 DA receptor agonist, altered evoked or spontaneous activity when ionophoretically applied. 3. Focal electrical stimulation in the region of the A11, but not the A9, DA cell group selectively suppressed nociceptive responses of spinal, multireceptive neurones in the rat. This stimulus-evoked effect was consistently and rapidly reversed by ionophoresis of sulpiride, in the vicinity of the dorsal horn neurone being tested. In contrast, naloxone and idazoxan (RX781094), an alpha 2-antagonist, were not effective. 4. This study presents data supporting a selective antinociceptive role for DA at the spinal level, where it has a widespread antinociceptive influence, on cells in both the superficial and deeper dorsal horn. The A11 DA cell group was shown to be a supraspinal site from which a selective antinociceptive action could be electrically evoked and which was mediated by DA at the level of the dorsal horn.
Fleetwood-Walker
S M
SM
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall.
Hope
P J
PJ
Mitchell
R
R
D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D000700:Analgesics; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D004298:Dopamine