Barry J. Sessle

Effects of substance P on nociceptive and non-nociceptive trigeminal brain stem neurons

&NA; As little information is available on the chemistry of synaptic transmission in trigeminal brain stem nuclei, an iontophoretic study was done on the effects of glutamate and substance P on single 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 units. 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 orafacial stimulation were not excited by substance P. Levorphanol and 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 transmission in nociceptive pathways in trigeminal nucleus caudalis. The regional specificity of substance P excitation adds support to the earlier evidence of a differential 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 parallels found between the dorsal horn and nucleus caudalis. In addition, the similarity between the dorsal horn and nucleus caudalis with respect to the effects of substance P and of the opioids suggests a parallel in the neurochemistry of synaptic transmission at the two levels.

Tooth pulp deafferentation is associated with alterations in functional properties of trigeminal (V) spinal tract neurones

Dentistry & Dept. of Physiology, Univ. of Toronto, Canada. Since deafferentation can result in the development of chronic Pain, and since dental deafferentation (e.g. extraction, endodontic therapy) is a common clinical procedure, we examined effects of pulp deafferentation on neurones in the V spinal tract nucleus, especially subnucleus oralis. Extracellular recordings were made from over 2,000 single neurones in chloralose-anaesthetized or decerebrated cats at a single post-operative time varying from 3 days to 2 years after endodontic removal of the coronal pulp of either the right maxillary or mandibular canine, premolar and molar teeth. Natural and electrical stimuli were applied to facial skin and intraoral sites. Compared with control animals, deafferentation was associated with a 50% reduction in the proportion of neurones having receptive fields localized within the V division containing the deafferented pulps, disruption of the normal inverted-head pattern of somatotopic organization, and 5-10 fold increases in the incidence of spontaneously active neurones and neurones with abnormal responses (e.g. discontinuous receptive field; habituation) to orofacial stimuli. The changes were especially apparent 7-15 days after pulp deafferentation, but alterations were apparent as long as 140 days after deafferentation; by 6 months, the changes were no longer obvious. The data indicate that partial deafferentation of a sensory input that is predominantly if not exclusively related to nociception (i.e. the dental pulp) can lead to marked functional changes in brainstem neurones of adult animals. Although the changes may be reversible, they raise the possibility that dental deafferentation may be a factor in the development of chronic orofacial pain conditions. (Supported by NIH grant DE 04786).

Evidence for opiate and non-opiate related descending influences on trigeminal (V) sensory and motor responses

EVIDENCE FOR OPIATE AND NON-OPIATE RELATED DESCENDING ] 267 Po INFLUENCES ON TRIGEMINAL (V) SENSORY AND MOTOR RESPONSES. I Thursday J.W. Hu, J.O. Dostrovsky and B.J. Sessle. Faculties of Medicine and Dentistry, Univ. of Toronto, Toronto, Ont., Canada Because of recent studies indicating the presence of a number of intrinsic descending influences on spinal nociceptive transmission, we have carried out a series of investigations on the effects of stimulation of numerous central sites on V sensory and motor responses. In anaesthetized or decerebrate cats, V spinal tract (VST) neurone and digastric, neck and respiratory tract reflex responses were evoked by noxious or non-noxious orofaeial stimuli and conditioned by stimulation of somatosensory cerebral cortex, periaqueductal gray (PAG), raphe magnus (NR~[), and adjacent regions including lateral reticular formation (IJiF) and nuclei reticularis gigantocellularis (RGC) and magnocellularis (RMC). PAG or NR>~ stimulation suppressed all 3 reflex responses and the activity of VSTneurones in subnuclei caudalis, interpolaris and ora]is evoked by tactile as well as tooth pulp and noxious facial stimuli, and also induced presynaptie excitability changes (PAD) of pulp,nociceptive and mechanoreceptive primary afferents. A contribution of endogenous opiaterelated mechanisms to some of these effects is suggested since naloxone partially reversed some suppressive effects on the reflexes and neurones, but the lack of PAD reversal by naloxone suggests that the opiate-related suppression may not involve PAD. The effects were not however restricted to PAG and NRM since reflex and VST neurone suppression and PAl) could be induced by cortex, LRF, RMC and RGC stimuli. Thus, V sensory and motor responses to non-nnxious as well as noxious stimuli are susceptible to numerous descending influences. Some of the descending influences from PAG ~ind N~M appear to involve endogenous opiaterelated mechanisms.