Neurons In Spinal Trigeminal Nucleus Research Articles

Effect of Restraint Stress on Pain Sensitivity, Spinal Trigeminal Nucleus Neurons, and Astrocytes in the Masseter Area of Rats.

To explore the changes of pain sensitivity (PS) in the masseter area (MA) in the rat model of psychological stress and the mechanism of action between spinal nucleus neurons and astrocytes in the trigeminal ganglion. The 40 Sprague-Dawley rats were randomly divided into control group (no treatment), group A (restraint stress (RS) 1 d), group B (RS 7 d), and group C (RS 14 d). The body weight growth rates (WGR) of rats in each group were compared and the difference of CORT and ACTH in serum was analyzed by ELISA. The open field test and the elevated “cross” maze test were adopted to detect the behavioral changes of rats. Finally, pain threshold of the MA in rats, the activation amount of brain tissue medulla oblongata parts astrocytes markers Glial fibrillary acidic protein (GFAP), and the protein expression of IL-1β and IL-1RI were detected. The results showed the WGR at 7 d and 14 d was greatly lower than control group (P < 0.01). In addition, the activity level and serum CORT and ACTH levels AND mean pain threshold in the MA of groups B and C were greatly lower than control group (P < 0.05). The activation rate of GFRP in group C (P < 0.01) and the protein expression of IL-1β and IL-1RI (P < 0.05) in rat trigeminal ganglion astrocytes of groups B and C was greatly higher than control group, indicating the increase of RS time, the release of IL-1β and IL-1RI can activate neurons and astrocytes in spinal trigeminal nucleus (STN) nerve and increase the PS of the MA.

Эффекты электромагнитного излучения миллиметрового диапазона на нейрональную активность спинального ядра тройничного нерва крысы

The study examined the effects of continuous low-intensity electromagnetic millimeter waves (MMW; frequency 40 GHz, power density of 0.04 mW/cm2) on ongoing firing of the spinal trigeminal nucleus (STN) neurons and their responses to the electrical stimulation of the dura mater in neurophysiological experiments on anesthetized rats. It is known that local exposure of MMW to certain areas of the skin can have a systemic therapeutic effect in the treatment of various pathologies. In particular, it concerns the use of MMW to treat headache of different genesis, with migraine being the most common form. The mechanisms of migraine are not clear, but it is known that the STN plays a key role in the migraine pathogenesis, providing the primary processing of pain signals from the cranial vessels as well as the transmission of these signals to overlying brain structures, in particular, to the thalamus. Recently, it has been reported that the frequency-modulated MMW causes short-term inhibitory changes in both the background activity of STN neurons and their responses to electrical stimulation of the dura mater. We assumed that the use of MMW in the unmodulated mode will allow to increase the duration of the MMW inhibitory effect on the background and evoked activity of STN neurons and thereby confirm potential antinociceptive action of MMW in migraine. The results of the present study have showed that the exposure of the STN neurons’ cutaneous receptive fields to unmodulated MMW is accompanied by prolonged cumulative inhibition of both the background activity of these neurons and their dural electrostimulation-evoked responses. The data allow considering these effects as an evindence in favour of potential antimigraine action of a continuous low-intensity MMW. It is proposed that the action can be based on the activation of nervous and immune processes in the skin, which, through a chain of neuronal mechanisms, can lead to a decrease in the excitability of STN neurons involved in the pathogenesis of migraine.

VGLUT1 or VGLUT2 mRNA-positive neurons in spinal trigeminal nucleus provide collateral projections to both the thalamus and the parabrachial nucleus in rats

The trigemino-thalamic (T-T) and trigemino-parabrachial (T-P) pathways are strongly implicated in the sensory-discriminative and affective/emotional aspects of orofacial pain, respectively. These T-T and T-P projection fibers originate from the spinal trigeminal nucleus (Vsp). We previously determined that many vesicular glutamate transporter (VGLUT1 and/or VGLUT2) mRNA-positive neurons were distributed in the Vsp of the adult rat, and most of these neurons sent their axons to the thalamus or cerebellum. However, whether VGLUT1 or VGLUT2 mRNA-positive projection neurons exist that send their axons to both the thalamus and the parabrachial nucleus (PBN) has not been reported. Thus, in the present study, dual retrograde tract tracing was used in combination with fluorescence in situ hybridization (FISH) for VGLUT1 or VGLUT2 mRNA to identify the existence of VGLUT1 or VGLUT2 mRNA neurons that send collateral projections to both the thalamus and the PBN. Neurons in the Vsp that send collateral projections to both the thalamus and the PBN were mainly VGLUT2 mRNA-positive, with a proportion of 90.3%, 93.0% and 85.4% in the oral (Vo), interpolar (Vi) and caudal (Vc) subnucleus of the Vsp, respectively. Moreover, approximately 34.0% of the collateral projection neurons in the Vc showed Fos immunopositivity after injection of formalin into the lip, and parts of calcitonin gene-related peptide (CGRP)-immunopositive axonal varicosities were in direct contact with the Vc collateral projection neurons. These results indicate that most collateral projection neurons in the Vsp, particularly in the Vc, which express mainly VGLUT2, may relay orofacial nociceptive information directly to the thalamus and PBN via axon collaterals.

Blockade of 5-HT3 receptors with granisetron does not affect trigeminothalamic nociceptive transmission in rats: Implication for migraine.

One way to expand the existing range of anti-migraine drugs seems to be the search for pharmacological agents with anti-cephalalgic properties among medicines approved for clinical indications other than migraine. Numerous experimental and clinical data imply that selective serotonin 5-HT3 receptor antagonists can be considered as potential anti-migraine agents. Therefore, the objective of our work was to examine the impact of selective 5-HT3 receptor blockade with granisetron on migraine-related nociceptive transmission within the spinal trigeminal nucleus (STN) and the ventroposteromedial nucleus of the thalamus (VPM). Using an electrophysiological model of trigemino-durovascular nociception in anaesthetised male Wistar rats, we evaluated the effects of intravenous administration of granisetron on ongoing firing and dural electrical stimulation-evoked responses of the spinal trigeminal and thalamic cells. Granisetron did not substantially affect responses of the STN and VPM neurons to electrical stimulation of the dura mater as well as did not cause steady changes in ongoing firing of the spinal trigeminal cells. The results obtained argue against the use of 5-HT3 receptor antagonists for treating migraine. These data also lead to the conclusion that in the absence of sustained sensitisation of neurons along the trigemino-thalamo-cortical pathway the role of 5-HT3 receptor-dependent mechanisms in serotonergic modulation of trigeminovascular nociceptive transmission can hardly be considered crucial.

Inhibitory effect of high-frequency greater occipital nerve electrical stimulation on trigeminovascular nociceptive processing in rats.

Electrical stimulation of the greater occipital nerve (GON) has recently shown promise as an effective non-pharmacological prophylactic therapy for drug-resistant chronic primary headaches, but the neurobiological mechanisms underlying its anticephalgic action are not elucidated. Considering that the spinal trigeminal nucleus (STN) is a key segmental structure playing a prominent role in pathophysiology of headaches, in the present study we evaluated the effects of GON electrical stimulation on ongoing and evoked firing of the dura-sensitive STN neurons. The experiments were carried out on urethane/chloralose-anesthetized, paralyzed and artificially ventilated male Wistar rats. Extracellular recordings were made from 11 neurons within the caudal part of the STN that received convergent input from the ipsilateral facial cutaneous receptive fields, dura mater and GON. In each experiment, five various combinations of the GON stimulation frequency (50, 75, 100Hz) and intensity (1, 3, 6V) were tested successively in 10min interval. At all parameter sets, preconditioning GON stimulation (250ms train of pulses applied before each recording) produced suppression of both the ongoing activity of the STN neurons and their responses to electrical stimulation of the dura mater. The inhibitory effect depended mostly on the GON stimulation intensity, being maximally pronounced when a stimulus of 6V was applied. Thus, the GON stimulation-induced inhibition of trigeminovascular nociceptive processing at the level of STN has been demonstrated for the first time. The data obtained can contribute to a deeper understanding of neurophysiological mechanisms underlying the therapeutic efficacy of GON stimulation in primary headaches.

CGRP Receptor Antagonism and Migraine Therapy

Migraine is the most prevalent of the neurological disorders and can affect the patient throughout the lifetime. Calcitonin gene-related peptide (CGRP) is a neuropeptide that is expressed in the central and peripheral nervous systems. It is now 2 decades since it was proposed to be involved in migraine pathophysiology. The cranial sensory system contains C-fibers storing CGRP and trigeminal nerve activation and acute migraine attacks result in release of CGRP. The CGRP receptor consists of a complex of calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1) and receptor component protein (RCP). At the central synapses in the trigeminal nucleus caudalis, CGRP acts postjunctionally on second-order neurons to transmit pain signals centrally via brainstem and midbrain to thalamus and higher cortical pain regions. CLR and RAMPs are widely expressed throughout the brain, in the trigeminal ganglion and in intracranial arteries. CGRP does not induce neurogenic inflammation or sensitization at peripheral meningeal sites but relays nociceptive information from trigeminal primary afferent neurons to the second-order neurons in the spinal trigeminal nucleus neurons. CGRP receptor antagonists have been developed as novel antimigraine drugs and found to be effective in the treatment of acute migraine attacks. Other ways to stop CGRP activity has been introduced recently through antibodies against CGRP and the CGRP receptor. While the CGRP receptors are expressed both in the CNS and at various places related to the trigeminal system the exact site of action for their therapy effect is still unresolved but the new approaches may resolve this.

Vagal afferent modulation of spinal trigeminal neuronal responses to dural electrical stimulation in rats

Vagus nerve stimulation (VNS) is an approved antiepileptic and antidepressant treatment, which has recently shown promise as a therapy for drug-resistant primary headaches. Specific neurobiological mechanisms underlying its anticephalgic action are not elucidated, partly because of the deficiency of research-related findings. The spinal trigeminal nucleus (STN) plays a prominent role in pathophysiology of headaches by modulating pain transmission from intracranial structures to higher centers of the brain. To determine whether vagal stimulation may affect trigeminovascular nociception, we investigated the effects of VNS on the STN neuronal activity in the animal model of headache. In anesthetized rats the spike activity of the STN neurons with convergent orofacial and meningeal inputs was monitored, and the changes in neuronal responses to electrical stimulation of the dura mater under preconditioning or under continuous electrical stimulation of the left cervical vagus nerve were studied. Preconditioning vagal afferent stimulation (200–ms train of pulses at 30Hz applied before each dural stimulus) did not produce substantial changes in the STN spike activity. However, continuous VNS with frequency of 10Hz in 48% of cases significantly suppressed trigeminal neuronal responses to dural electrical stimulation. In line with the decrease in evoked activity, the VNS-induced depression of ongoing neuronal firing was observed. Although the inhibitory effect was prevailing, 29.5% of STN neurons were facilitated by VNS, whereas 22.5% were unresponsive to the stimulation. These results provide an evidence of VNS-induced modulation of trigeminovascular nociception, and therefore contribute to a deeper understanding of neurophysiological mechanisms underlying effects of vagal stimulation in chronic drug-resistant headaches.

The Nonpeptide Calcitonin Gene-Related Peptide Receptor Antagonist BIBN4096BS Lowers the Activity of Neurons with Meningeal Input in the Rat Spinal Trigeminal Nucleus

Calcitonin gene-related peptide (CGRP) has been suggested to play a major role in the pathogenesis of migraines and other primary headaches. CGRP may be involved in the control of neuronal activity in the spinal trigeminal nucleus (STN), which integrates nociceptive afferent inputs from trigeminal tissues, including intracranial afferents. The activity of STN neurons is thought to reflect the activity of central trigeminal nociceptive pathways causing facial pain and headaches in humans. In a rat model of meningeal nociception, single neuronal activity in the STN was recorded. All units had receptive fields located in the exposed parietal dura mater. Heat and cold stimuli were repetitively applied to the dura in a fixed pattern of ramps and steps. The nonpeptide CGRP receptor antagonist BIBN4096BS was topically applied onto the exposed dura or infused intravenously. BIBN4096BS (300 microg/kg, i.v.) reduced spontaneous activity by approximately 30%, the additional dose of 900 microg/kg intravenously by approximately 50% of the initial activity, whereas saline had no effect. The activity evoked by heat ramps was also reduced after BIBN4096BS (900 microg/kg, i.v.) by approximately 50%. Topical administration of BIBN4096BS (1 mm) did not significantly change the spontaneous neuronal activity within 15 min. We conclude that the endogenous release of CGRP significantly contributes to the maintenance of spontaneous activity in STN neurons. Blockade of CGRP receptors, possibly at central and peripheral sites, may therefore be an effective way to decrease nociceptive transmission. This may offer a new therapeutic strategy for the treatment of facial pain and primary headaches.

Nitric oxide synthase inhibition lowers activity of neurons with meningeal input in the rat spinal trigeminal nucleus.

Nitric oxide is thought to control transmitter release and neuronal activity in the spinal dorsal horn and the spinal trigeminal nucleus, where nociceptive information from extra- and intracranial tissues is processed. Extracellular impulse activity was recorded from neurons in the rat spinal trigeminal nucleus with afferent input from the cranial dura mater. In contrast to the inactive isomer D-NAME, infusion of the nitric oxide synthase inhibitor L-NAME (20 mg/kg) significantly reduced neuronal activity and increased systemic blood pressure. It is concluded that nitric oxide production contributes to the ongoing activity of sensitized neurons in the spinal trigeminal nucleus. The results suggest that nitric oxide may be involved in the generation and maintenance of primary headaches such as migraine.

Mechanisms and predictors of chronic facial pain in lateral medullary infarction

The purpose of this study was to identify clinical predictors and anatomical structures involved in patients with pain after dorsolateral medullary infarction. Eight out of 12 patients (67%) developed poststroke pain within 12 days to 24 months after infarction. The pain occurred in the ipsilateral face (6 patients) and/or the contralateral limbs and trunk (5 patients, 3 of whom also had facial pain). Ipsilateral facial pain was significantly correlated with lower medullary lesions, including those of the spinal trigeminal tract and/or nucleus, as documented by magnetic resonance imaging. The R2 blink reflex component was abnormal only in patients with facial pain. Likewise, pain and temperature sensation in the ipsilateral face was decreased in all patients with facial pain but not in patients without pain. Ipsilateral touch sensation in the face was also decreased in all patients with facial pain, but the lesions revealed on magnetic resonance imaging did not involve the principal sensory nucleus of the fifth cranial nerve, and the R1 blink reflex latencies were normal. Although facial pain was correlated with lesions of the spinal trigeminal tract and/or nucleus, none of the lesions involved the subnucleus caudalis, which contains most nociceptive neurons. These findings suggest that facial pain after medullary infarction is due to lesions of the lower spinal trigeminal tract (axons of primary afferent neurons), leading to deafferentation of spinal trigeminal nucleus neurons.

Single neurons in the spinal trigeminal and dorsal column nuclei project to both the cochlear nucleus and the inferior colliculus by way of axon collaterals: a fluorescent retrograde double-labeling study in the rat

A number of single neurons in the spinal trigeminal nucleus (STN) and the dorsal column nucleus (DCN) were found to project simultaneously to the cochlear nucleus (CoN) and the external cortex of the inferior colliculus (ICe) by way of axon collaterals. Each rat was injected with Fluoro-Gold (FG) into CoN on one side and with tetramethylrhodamine-dextran amine (TMR-DA) into ICe on the side ipsilateral or contralateral to the FG injection. In these rats, a number of neuronal cell bodies in DCN and the interpolar and caudal subnuclei of STN were double-labeled retrogradely with both FG and TMR-DA, mainly on the side ipsilateral to the FG injection into CoN. These neurons in STN and DCN might mediate somatosensory inputs simultaneously to the two lower brainstem nuclei, CoN and ICe, which constitute the relays of the auditory pathway.

Different sensitivity to hypoxia in neuronal activities of lateral vestibular and spinal trigeminal nuclei.

Electrophysiologic studies were performed to examine the effects of hypoxia on neuronal activities of the lateral vestibular and spinal trigeminal nuclei using rats anesthetized with chloral hydrate. The rats inhaled a gas mixture of 5% oxygen and 95% nitrogen for 3.5 minutes to induce hypoxia, followed by room air. Under these conditions, mean PaO2 was decreased from 85 to 22 mm Hg 3 minutes after the start of the inhalation concomitant with a decrease in blood pressure from 108 to 55 mm Hg. There were no significant differences in these variables between rats used for vestibular nucleus experiments and rats used for trigeminal nucleus experiments. In the lateral vestibular nucleus, hypoxia inhibited postsynaptic components of the evoked field potential, spike generation of monosynaptic neurons on vestibular nerve stimulation, and firing induced by iontophoretic application of glutamate. In the spinal trigeminal nucleus, however, there were no alterations of the field potential or spike generation of the neurons on trigeminal nerve stimulation. These results indicate that the lateral vestibular nucleus neurons are much more sensitive to hypoxia than the spinal trigeminal nucleus neurons. The failure of transmission in the monosynaptic neurons of the lateral vestibular nucleus is suggested to be due to the inhibition of excitability of the postsynaptic membrane.

A quantitative light microscopic analysis and ultrastructural description of cholecystokinin-like immunoreactivity in the spinal trigeminal nucleus of the rat

The spinal trigeminal nucleus is involved in orofacial sensory transmission. Cholecystokinin octapeptide has been identified in axons in this nucleus and appears to play a role in the transmission of orofacial sensation from the trigeminal ganglia to the spinal trigeminal nucleus. Although cholecystokinin has been reported in axonal processes within the spinal trigeminal nucleus at the light microscopic level, nothing is known about the synaptic relationships of these cholecystokinin axons. The goals of this study were to quantitatively determine the volume fraction of cholecystokinin-like immunoreactive cell bodies and fibers in the three subnuclei of the spinal trigeminal nucleus, to provide the first ultrastructural description of cholecystokinin-like immunoreactive processes within these subnuclei and to analyse the synaptic relationships of cholecystokinin-like immunoreactive processes within the spinal trigeminal nucleus neuropil. Cholecystokinin-like immunoreactivity was localized by the peroxidase-antiperoxidase method or the peroxidase labeled, avidin-biotin technique and quantified at the light microscopic level by point counting. Immunoreactive fibers were present in all three subnuclei, but the greatest volume fraction of immunoreactive axons was obtained in laminae I and II of the nucleus caudalis. No immunoreactive cell bodies were evident in any of the subnuclei. The majority of immunoreactive profiles in all three subnuclei were identified ultrastructurally as axon terminals that contained both small and medium sized agranular vesicles and infrequently, large dense core vesicles. These immunoreactive terminals were usually found in close contact with non-immunoreactive dendrites with which they were observed to form asymmetric synapses. Immunoreactive terminals were occasionally observed to contact the cell bodies of large non-immunoreactive neurons on the border of laminae I and II in the nucleus caudalis. These results indicate that cholecystokinin-like immunoreactive processes are present throughout the spinal trigeminal nucleus and in nucleus caudalis show a distribution similar to that reported for the spinal cord dorsal horn. Immunoreactive axons make synaptic contact with both the dendrites and perikarya of spinal trigeminal nucleus neurons. No axoaxonic synapses were observed. These findings suggest that cholecystokinin plays an important role in spinal trigeminal nucleus function. The possible colocalization of cholecystokinin and substance P in the spinal trigeminal nucleus and the possible role of cholecystokinin in attenuating the action of opioids in the spinal trigeminal nucleus are also discussed.

Beta-receptor involvement in locus coeruleus-induced inhibition of spinal trigeminal nucleus neurons: Microiontophoretic and HRP studies

Microiontophoretic and HRP studies were performed on cats anesthetized with α-chloralose to determine whether or not the locus coeruleus (LC)- and noradrenaline (NA)-induced inhibition of relay neurons in the subnucleus oralis of the spinal trigeminal nucleus (STN) is mediated by ß-adrenergic receptors. The inhibition of orthodromic spike generation upon intracranial trigeminal nerve stimulation by LC conditioning stimulation and microiontophoretically applied NA (100–200 nA) was antagonized during microiontophoretic application of sotalol, a ß-adrenergic, but not affected by phentolamine, an α-adrenergic antagonist. When HRP at doses of 300–500 nA was applied for 5–15 min to the immediate vicinity of the STN relay or interneuron, which was electrophysiologically identified by stimulating the ipsilateral trigeminal nerve and contralateral medial lemniscus, the injection site was localized to an area 0.3 mm in diameter and HRP-reactive cells were found in the ipsilateral LC, dorsal raphe nucleus and periaqueductal gray ventral to the aqueduct. These results strongly suggest that NA released from the nerve terminals of LC cells inhibits transmission in the STN relay neuron via ß-adrenergic receptors.

Co-localization of fixative-modified glutamate and glutaminase in neurons of the spinal trigeminal nucleus of the rat: an immunohistochemical and immunoradiochemical analysis.

The spinal trigeminal nucleus (STN) is involved in processing orofacial sensory information, including tactile, thermal and nociceptive input, and relaying this information to higher brain centers, such as the thalamus. Very little information is available regarding the major excitatory neurotransmitters of this nucleus. The amino acid glutamate has been proposed as a major excitatory neurotransmitter in the central nervous system. In the present study, a novel monoclonal antibody, specific for fixative-modified glutamate, was utilized in conjunction with polyclonal antisera against glutaminase and aspartate aminotransferase (AATase) in an attempt to identify and map the locations of possible glutamatergic neurons in the STN. Co-localization experiments were performed by radiolabeling our monoclonal antibody and using this antibody in conjunction with the polyclonal antisera against glutaminase and AATase to evaluate the possible coexistence of glutamate with glutaminase or AATase in STN neurons. In all three subnuclei of the STN, immunohistochemically labeled neuronal profiles were observed with both of the polyclonal antisera and with the monoclonal antibody. Subnucleus caudalis contained the greatest number of labeled profiles per coronal section followed by subnucleus interpolaris and subnucleus oralis. The number and the distribution of immunoreactive profiles observed after the use of the glutaminase antiserum was comparable to that obtained with the monoclonal antibody. Co-localization experiments demonstrated that all glutaminase-like immunoreactive neurons also contained fixative-modified glutamate-like immunoradioactivity. These results suggest that glutamatergic neurons are present in the spinal trigeminal nucleus. The AATase antiserum labeled more neuronal profiles in each of the three subnuclei than did the glutaminase antiserum or the monoclonal antibody. In addition, co-localization experiments indicated that glutamate-like immunoreactivity was present in only two-thirds of AATase-like immunoreactive neuronal profiles. These findings suggest that glutaminase may be a more reliable marker of glutamatergic function than AATase.

Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat Neurol. 186 (1979)_133–150 : S. Igarashi, M. Sasa and S. Takaori, Brain Res. Bull., 4 (1979) 75–83

Pain: February 1980 - Volume 8 - Issue 1 - p 125-126 doi: 10.1016/0304-3959(80)90103-7

Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat

IGARASHI, S., M. SASA AND S. TAKAORI. Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat. BRAIN RES. BULL. 4(1) 75–83, 1979.—Studies were performed to elucidate reciprocal relationships between locus coeruleus (LC) and spinal trigeminal nucleus (STN) neurons responding to tooth pulp (TP) stimulation using rats anesthetized with α-chloralose. LC conditioning stimulation inhibited STN field potential as well as orthodromic spike generation of STN neurons produced by ipsilateral TP stimulation, confirming the previous findings in cats that LC neurons played an inhibitory role in the orthodromic transmission in STN neurons. Forty-one out of 56 LC neurons were activated by ipsilateral TP stimulation and 12 neurons by stimulation of both ipsi- and contralateral TP. STN stimulation usually excited LC neurons with a significantly shorter latency than did TP stimulation, including three LC neurons with a latency of less than 2.0 msec. These results indicate the existence of input from TP to LC neurons via multisynapses. In addition, neurons antidromically activated by STN stimulation were found in LC. It is highly probable, therefore, that there is a feedback loop between LC and STN, which might control input from TP to STN.

β-Receptor in noradrenergic inhibition of spinal trigeminal nucleus neurons

β-Receptor in noradrenergic inhibition of spinal trigeminal nucleus neurons

Dorsal raphe stimulation produces inhibitory effect on trigeminal nucleus neurons

Inhibitory effects of conditioning stimulation of the dorsal raphe nucleus (DR) on the neuron activity in the rostral part of spinal trigeminal nucleus (STN) were studied in cats for the purpose of comparison with the inhibition induced by locus coeruleus (LC) stimulation. DR conditioning stimulation reduced the orthodromic field potential in STN elicited by inferior alveolar nerve stimulation, and enhanced the antidromic field potential in the trigeminal nerve evoked by STN stimulation; but the inhibitory effects of DR stimulation were considerably weaker than those of LC stimulation. In tracking experiments near the raphe nucleus, conditioning stimulation of DR itself produced the most pronounced decrease in the STN field potential. Orthodromic spike number of STN relay neurons was significantly reduced by DR conditioning stimulation; however, the threshold for the conditioning stimulus to the DR was much higher than that to the LC. Antidromic spike generation of the STN neurons was unaltered by conditioning stimulation of both DR and LC. DR stimulation elicited a field potential in STN, which followed high frequency stimuli up to 200 Hz. A single fiber action potential was also obtained in STN by DR stimulation. STN stimulation produced a field potential in DR, which followed high frequency stimuli. It is suggested from these findings that conditioning stimulation of DR produces a direct inhibition of transmission in STN neurons; however, this stimulation has less effect on these neurons than does stimulation of the LC.

Morphine interference with noradrenaline-mediated inhibition from the locus coeruleus

The effect of morphine on inhibition of relay neurons in the spinal trigeminal nucleus (STN) produced by conditioning stimulation of the locus coeruleus (LC) was studied in cats. Alterations in orthodromic and antidromic spike generations in STN were absent. However, the narcotic did selectively reduce the inhibitory effect of LC conditioning stimulation on STN neurons without affecting that of the sensory ortex. Nalorphine partially antagonized this effect of the narcotic. A reduction in orthodromic spike number of STN neurons induced by intraventricular noradrenaline in reserpinized animals was unaltered by morphine treatment. These data demonstrate that morphine selectively interferes with LC-induced inhibition of STN neurons and in addition may block noradrenaline release from terminals of LC neurons.