Pain, 8 (1980) 33--45 © Elsevier/North-Holland Biomedical Press 33 EFFECTS OF SUBSTANCE P ON NOCICEPTIVE AND NON-NOCICEFHVE TRIGEMINAL BRAIN STEM NEURONS JAMES L. HENRY *, BARRY J. SESSLE, GREGORY E. LUCIER and JAMES W. HU (J.L.H.) Department of Research in Anaesthesia, McGill University, Montreal H3G 1 Y6, and Division of Biological Sciencem, Faculty of Dentistry, University of Toronto, Toronto M5G I G6 (Canodu) (Accepted November 9th, 1979) SUMMARY As little information is available on the chemistry of synaptic transmis- sion in trigeminal brain stem nuclei, an iontophoretic study was done on the effects of ghltamate and substance P on singie neurons in trigeminal nuclei oralis and caudalis in cats anesthetized with chloralose and paralyzed. The neurons were additionally studied for their responses to natural noxious and innocuous cutaneous and intraoral stimuli as well as to bipolar stimulation of the ipsilateral and contralateral canine tooth pulps, the exposed infraorbital and superior laryngeal nerves and forepaw. Glutamate excited all units tested. Substance P also had an excitatory effect, but only on some vnits. The slow time course of this effect was similar to that reported in other CNS regions. Units excited by substance P were located only in nucleus caudalis, and all responded to noxious cutaneous stimuli and/or to stimulation of tooth pulp; units responding only to innocuous orofacial stimulation were not excited by substance P. Levorphanol azLd opioid peptides were also applied iontophoretically to some of the neurons and were found to have depressant effects on nociceptive units. The data support the possibility that substance P and endogenous opioids play a role in chemical transmissic, n in nociceptive pathways in trigemlnal nucleus caudalis The regional specificity of substance P excitation adds support to the earlier evidence of a differen- tial distribution of sensory inputs to nuclei oralis vs. caudalis, with facial nociceptive afferents projecting only to caudalis. The functional specificity of substance P excitation also adds to the parallelsfound between the dorsal horn and nucleas caudaiis. In addition, the similarity between the dorsal * Pleue send correspondence to: Dr. James L. Henry, Department of Research in An- aesthesia, McGill University, 3655 D r u m m o n d Street, Montreal, Quebec H3G 1Y6, Canada.