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 nucleusneurons 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.     

Inhibitory controls on thermal neurones in the spinal trigeminal nucleus of cats and rats

Although electrical stimulation of supraspinal structures and local large fibres is known to inhibit the responses of nociceptive neurones, comparable studies on thermoreceptive cells have not been made. We have studied the effects of nucleus raphe magnus (NRM) and segmental stimulation on cold and warm responsive neurones in trigeminal nucleus caudalis of both the rat and cat. All 48 neurones (46 cold and 2 warm) tested in the cat and 24 cold neurones in the rat were unaffected by the NRM at a variety of stimulation parameters. However, segmental stimulation inhibited420 neurones in the cat and1126 cells in the rat. The results show the selectivity of the inhibition following NRM stimulation.     

Tooth pulp input to the spinal trigeminal nucleus: A comparison of inhibitions following segmental and raphe magnus stimulation

In rats and cats anaesthetized with urethane a comparison was made of the inhibitory effects of raphe magnus (NRM) and segmental (facial skin) stimulation on neurones in nucleus caudalis excited by tooth pulp stimulation. The upper and lower ipsilateral incisor teeth were used in rats (176 neurones) and the corresponding canine teeth in cats (34 neurones). The recording sites were located in all layer of nucleus caudalis and in the underlying reticular formation. Both the evoked responses and the conditioning effects were similar in the two species. Both forms of conditioning inhibited about half the neurones tested but only a small proportion was influenced from both sources. NRM stimulation had almost identical effects on neurones driven from upper teeth or from lower teeth and tended to act on those cells with longer latencies. Segmental stimulation influenced the majority of shorter latency cells and produced greater inhibitions of upper tooth pulp neurones. Diffuse noxious inhibitory controls were also observed for certain neurones.     

Electroacupuncture suppression of the rat jaw opening response after stimulating the caudal spinal trigeminal nucleus

Suppressive effects of electroacupuncture on the jaw opening responses evoked by stimulation of two areas (anterior and posterior) within the caudal spinal trigeminal nucleus were investigated using lightly anesthetized rats. Electroacupuncture stimulation markedly suppressed the jaw opening responses evoked by stimulating the posterior area, but suppressed only slightly those evoked by stimulating the anterior area.     

Effects of various frequency electrical stimulation of the dorsal raphe nucleus on spontaneous firing activities in the rat subthalamic nucleus★

BACKGROUND： Some investigations have demonstrated that exogenous 5-hydroxytryptamine increases the spontaneous firing rate of subthalamic nucleus （STN） neurons in the rat brain. OBJECTIVE： To validate the effect of electrical stimulation to the dorsal raphe nucleus （DRN） on the neuronal activities of the STN in rats, as well as analyze the differences in the effects of electrical stimulation at various frequencies. DESIGN, TIME AND SETTING： Experiments were performed from March 2007 to June 2007 in the Electrophysiology Laboratory of Liaoning Medical University with a randomized controlled animal study design. MATERIALS： Twenty-four healthy male Sprague-Dawley （SD） rats, weighing 250-350 g, were selected for this study. An A320R constant electrical stimulator was purchased from World Precision Instruments Company （USA）; a Spike 2 biological signal acquisition system was purchased from British CED Company. METHODS： Twenty-four SD rats were randomly assigned into a model group and a normal group, with 12 rats in each group. To mimic Parkinson＇s disease, rats in the model group were injected with 4μL of 6-hydroxydopamine into the right striatum, then received deep brain stimulation. Rats in the normal group received deep brain stimulation in same brain region without modeling. Electrical stimulation （width, 0.06 ms; intensity, 0.2-0.6 mA; frequency, 20-130 Hz; train duration, 5 seconds） was delivered to the DRN. MAIN OUTCOME MEASURES： The firing rates of STN neurons were observed by extracellular recording using a biological signal acquisition system. RESULTS： DRN-high-frequency stimulation （DRN-HFS） induced excitation in 59% of the STN neurons in the normal group and 50% of the STN neurons in the model group; mean firing rates increased significantly from （7.14±0.75） and （7.94 ± 0.61） Hz to （11.17 ±1.49） and （12.11 ± 1.05） Hz, respectively （P 〈 0.01）. Spontaneous firing rate increased significantly in 53% of neurons in normal rats in a frequency-dep     

Wind-up of tooth pulp-evoked responses and its suppression in rat trigeminal caudal neurons

Induction and suppression of wind-up were studied in 97 tooth pulp-driven neurons in the trigeminal subnucleus caudalis, using Wistar albino rats anesthetized with urethane and alpha-chloralose. Tooth pulp stimulation applied to an ipsilateral lower incisor evoked early discharges, indicating excitatory inputs from A-delta fibers and subsequent late discharges from C-fiber volleys in caudal neurons. Wind-up was efficiently evoked by stimulation delivered at 0.3-1 Hz, with current intensity sufficient to evoke late discharges. Conditioning stimulation of the arcuate nucleus of the hypothalamus (ARH) suppressed late discharges, including wind-up, without affecting the A-fiber response. Focal cooling of the periaqueductal gray (PAG) abolished the suppression by the ARH and further enhanced the wind-up of the caudal neurons. These results suggest: 1) Temporal summation of depolarization evoked by C-fiber volleys builds wind-up in caudal neurons; 2) ARH stimulation suppresses late discharges by blocking synaptic transmission from C-fiber inputs, and this interrupts prolonged facilitation of the neurons; 3) the ARH is involved in induction of inhibitory controls descending from the PAG to the trigeminal caudalis.     

Suppression of tooth pulp evoked responses by activation of raphe-trigeminal neurons in rat

IRIKI, A. AND K. TODA. Suppresion of tooth pulp evoked responses by activation of raphe-trigeminal neurons in rat. BRAIN RES. BULL. 8(6) 777–780, 1982.—Electrical stimulation (0.1 msec duration, 50 Hz, l min) applied to the nucleus raphe magnus markedly suppressed the tooth pulp evoked responses in caudal part of the spinal trigeminal nucleus but only slightly altered those in its rostral area. Raphe stimulation also greatly suppressed jaw opening reflex evoked by tooth pulp stimulation, which lasted longer than suppression of spinal trigeminal nucleus.     

Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin re- ceptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal trigeminal nucleus and trigeminal ganglion was determined with immunohistochemistry and histo- chemistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings sug- gest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin＇s regulatory effect on pain is attenuated.     

电刺激大鼠杏仁中央核对脑桥臂旁核味觉神经元的影响(英文)

利用电生理学方法观察了电刺激杏仁中央核对脑桥臂旁核味觉神经元的影响。结果表明 :电刺激杏仁中央核抑制大部分臂旁核味觉神经元的活动 ,并且提高臂旁核味觉神经元对五种基本味觉刺激反应的特异性。电刺激杏仁中央核对臂旁核的抑制作用以对盐酸和奎宁刺激的反应尤为明显 (P <0 .0 1) ,并且对这两种厌味刺激反应的抑制作用是基本一致的。本研究的结果提示 ,杏仁中央核可能通过抑制脑干味觉神经元对厌味刺激的反应 ,从而参与对摄食行为的调控     

电刺激大鼠杏仁中央核对脑桥臂旁核味觉神经元的影响

利用电生理学方法观察了电刺激杏仁中央核对脑桥臂旁核味觉神经元的影响.结果表明:电刺激杏仁中央核抑制大部分臂旁核味觉神经元的活动,并且提高臂旁核味觉神经元对五种基本味觉刺激反应的特异性.电刺激杏仁中央核对臂旁核的抑制作用以对盐酸和奎宁刺激的反应尤为明显(P＜0.01),并且对这两种厌味刺激反应的抑制作用是基本一致的.本研究的结果提示,杏仁中央核可能通过抑制脑干味觉神经元对厌味刺激的反应,从而参与对摄食行为的调控.     

Evidence for involvement of separate mechanisms in the production of analgesia by electrical stimulation of the nucleus reticularis paragigantocellularis and nucleus raphe magnus in the rat

The effect of ambient temperature (T_A) on the rectal temperature (T_RE) response to intraventricular injection of bombesin has been evaluated in conscious adult male rats. AtT_A= 4 °C, bombesin (50 ng-1 μg) caused a marked hypothermia which was dose-dependent both in terms of the magnitude and of the duration of the response. The bombesin-induced hypothermia was reduced atT_A= 24 °C, whereas atT_A= 31 or 33 °C, the peptide (1 μg) failed to affect T_RE. AtT_A= 36 °C, bombesin 1–10 μg induced anelevation in T_RE. The hyperthermia observed at high T_A could be reversed to hypothermia by transferring rats to cold. The analogs [D-Trp⁸]bombesin or [D-Leu¹³]-bombesin, tested under the same conditions, failed to produce significant changes in T_RE. These findings demonstrate that bombesin appears to act in the brain as a poikilothermic agent by disrupting thermoregulation at temperatures below or above thermoneutrality.     

Effect of systemic nitroglycerin on CGRP and 5-HT afferents to rat caudal spinal trigeminal nucleus and its modulation by estrogen

Systemic administration of nitroglycerin, a nitric oxide donor, triggers in migraine patients a delayed attack of unknown mechanism. After puberty migraine is more prevalent in women. Attacks can be triggered by abrupt falls in plasma estrogen levels, which accounts in part for sexual dimorphism, but lacks an established neurobiological explanation. We studied the effect of nitroglycerin on the innervated area of calcitonin gene-related peptide (CGRP) and serotonin-immunoreactive afferents to the superficial laminae of the spinal portion of trigeminal nucleus caudalis, and its modulation by estrogen. In male rats, nitroglycerin produced after 4 h a significant decrease of the area innervated by CGRP-immunoreactive afferents and an increase of that covered by serotonin-immunoreactive fibres. These effects were not observed in the superficial laminae of thoracic dorsal horns. The effect of nitroglycerin was similar in ovariectomized females. In estradiol-treated ovariectomized females the area in the spinal portion of trigeminal nucleus caudalis laminae I-II covered by CGRP-immunoreactive fibres was lower and that of serotonin-immunoreactive fibres was higher than in males and for both transmitters not significantly changed after nitroglycerin. The bouton size of CGRP profiles was smaller in estradiol-treated ovariectomized females, whereas after nitroglycerin it decreased significantly but only in males and ovariectomized females. Nitroglycerin, i.e. nitric oxide, is thus able to differentially influence afferent fibres in the superficial laminae of rat spinal trigeminal nucleus caudalis. Estradiol modulates the basal expression of these transmitters and blocks the nitroglycerin effect. These data may contribute to understanding the mechanisms by which estrogens influence migraine severity and the triggering of attacks by nitric oxide.     

Edinger-Westphal nucleus: cholecystokinin immunocytochemistry and projections to spinal cord and trigeminal nucleus in the cat

Immunocytochemical methods were used to determine the distribution of cells with cholecystokinin-like immunoreactivity (CCK-LI) in the cat Edinger-Westphal complex (EW). Numerous cells with CCK-LI are found throughout the length of EW. The distribution and frequency of such cells are similar to the pattern of EW neurons that show substance P-like immunoreactivity (SP-LI). Companion retrograde transport experiments reveal that EW neurons which project to spinal cord or the region of the caudal trigeminal nucleus are found throughout the length of EW, and that some EW neurons which project to spinal cord also show CCK-LI.     

Phosphorylation of Extracellular Signal-Regulated Kinase in medullary and upper cervical cord neurons following noxious tooth pulp stimulation

The phosphorylated Extracellular Signal-regulated Kinase (pERK) and Fos expression and masticatory muscle activity were analyzed in rats with capsaicin-induced acute inflammation of the tooth pulp in order to clarify the role of the spinal trigeminal nucleus and upper cervical spinal cord in tooth pulp pain. Digastric and masseteric muscle activities were significantly increased following capsaicin injection into the molar tooth pulp but not after vehicle treatment. The pERK-like immunoreactive (LI) neurons were observed in the subnuclei interpolaris-caudalis transition (Vi/Vc) zone, the paratrigeminal nucleus (Pa5) and the superficial laminae of the caudal Vc/C2 zone. The pERK expression was detected as early as 2 min and peaked at 5 min after capsaicin or vehicle injection. The pERK expression in the Vi/Vc zone and Pa5 was bilateral, whereas it was predominantly ipsilateral in the caudal Vc/C2 zone. The capsaicin treatment of the whisker pad produced pERK expression in the rostro-caudal middle portion of the ipsilateral Vc, but small number of pERK-LI cells were observed after vehicle treatment. The pERK expression was similar in the Vi/Vc zone following capsaicin injection into the upper or lower molar tooth pulp, whereas the pERK expression was in the lateral portion of the caudal Vc/C2 zone after upper molar injection and restricted to the medial portion of the Vc/C2 zone after the lower molar capsaicin. These data were confirmed with Western blots. There were differences in the distribution of Fos protein-like immunoreactive (LI) cells and pERK-LI cells following tooth pulp stimulation. After capsaicin application into the upper molar tooth pulp, no pERK-LI cells were observed in the ventral part of the Vi/Vc zone, whereas many Fos protein-LI cells were expressed in this region. The difference in the distribution pattern of pERK- and Fos protein-LI cells in the Vi/Vc zone suggests their differential temporal expression profiles after capsaicin. The present findings suggest that tooth-pulp-driven neurons in the spinal trigeminal nucleus are involved in tooth pulp pain through activation of the intracellular signal transduction pathway that involves earlier ERK phosphorylation and subsequent Fos expression.     

Inhibitory effect of stimulation of the anterior pretectal nucleus on the jaw-opening reflex

The anterior pretectal nucleus (APT) has been recently implicated in sensorimotor integration and has been shown to have suppressive influences on tail flick behaviour and on nociceptive responses of spinal dorsal horn neurones in rats. The present study tested the effect of stimulation of the APT on the rat's digastric jaw-opening reflex elicited by orofacial stimuli. Either ipsilateral or contralateral electrical stimulation at histologically confirmed sites within and immediately subjacent to the APT produced a suppression of the reflex that had an onset of 20–30 ms, peaked around 50 ms and lasted for 200–300 ms; in some cases, a brief period of reflex facilitation preceded the onset of inhibition was sometimes followed by a facilitatory period. No prolonged period of suppression induced by electrical stimulation was noted in these anaesthetized rats. The injection of monosodium glutamate at comparable sites within and subjacent to APT induced reflex suppression that lasted several minutes. These findings represent the first documentation of APT-induced modulation in the trigeminal sensorimotor system, but support recent evidence suggesting the involvement of APT in sensorimotor integration and modulation.     

Analgesia produced by electrical stimulation of the brain

1. Electrical stimulation of the brain can produce a selective and potent modulation of responding to noxious stimuli in animals and man. The influence of various stimulation parameters is discussed.

2. Brain stimulation at numerous loci results in analgesia. The most well characterized regions are the mesencephalic periaqueductal gray matter and the medullary raphe nuclei.

3. One pain inhibitory system activated by brain stimulation involves a neural circuit from the PAG to the medullary raphe nuclei. Output from there descends via the DLF to modulate pain transmission in the dorsal horn of the spinal cord. Other analgesia systems are also activated by brain stimulation.

4. Compelling evidence implicates endogenous opiates in SPA. Monoaminergic neurotransmitters are also involved in SPA.

5. Brain stimulation has proven to be useful for the management of some forms of intractable pain in man.     

Trigeminal ganglion neurons which project by way of axon collaterals to both the caudal spinal trigeminal and the principal sensory trigeminal nuclei

Employing a combination of fluorescent retrograde double labeling and immunofluorescence histochemistry, we found that some single neurons in the trigeminal ganglion of the rat projected by way of axon collaterals both to the caudal spinal trigeminal nucleus and to the principal sensory trigeminal nucleus, and that about 40% or 57% of these neurons showed respectively substance P- or calcitonin gene-related peptide-like immunoreactivity.     

Dopamine-immunoreactivity in the rat mesencephalic trigeminal nucleus: an ultrastructural analysis

The ultrastructure and distribution of dopaminergic boutons within the rat mesencephalic trigeminal (Me5) nucleus was examined with the use of electronmicroscopic immunocytochemistry. A total of 5102 boutons, comprising axosomatic and axodendritic synaptic terminals as well as non-synaptic boutons (or varicosities), located in the ventrocaudal portion of Me5 was analysed. Approximately 20% of these boutons were dopamine-immunoreactive. Morphological analysis showed that the dopaminergic synaptic terminals, axodendritic as well as axosomatic, were exclusively of the S- and G-bouton type; they contained, respectively, small spherical vesicles or small pleomorphic vesicles in combination with large granular dense-cored vesicles. All dopaminergic varicosities in the Me5 were of the G-bouton type. Quantitative analysis revealed that most of the dopaminergic synaptic terminals in the Me5 nucleus contacted dendrites, while only a minority (12%) contacted Me5 somata. This dopaminergic somatic input comprised about half (52%) of the total axosomatic input on Me5 neurons. The present results and previous findings with respect to the prominent serotonergic component of the axosomatic input to Me5 neurons indicate that dopamine and serotonin account for most of the axosomatic input in the ventrocaudal part of the Me5 nucleus. In fact, the present results seem to support previous observations regarding the existence of a population of afferent neurons in which dopamine and serotonin are colocalized.     

Response characteristics of primary periodontal mechanoreceptive neurons in the trigeminal mesencephalic nucleus to trapezoidal mechanical stimulation of a single tooth in the rat

The response characteristics of primary periodontal mechanoreceptive neurons in the trigeminal mesencephalic nucleus (MeNV) were studied by changing the rate and magnitude of trapezoidal pressure applied to the upper incisor in very lightly anesthetized rats.Using a metal microelectrode in the MeNV either for recording or for stimulation, the projection site of primary afferents in the anterior superior alveolar nerve innervating the upper incisor was determined. Its stereotaxic coordinates were 1.0–2.0 mm posterior to the interaural plane and 1.2–1.3 mm lateral to the mid-sagittal plane, corresponding to the caudal part of the MeNV.From this site of 19 animals, single unitary activity from 41 primary periodontal mechanoreceptive neurons was recorded, which were identified by: (1) the constant, brief latency of 1.0–4.0 ms (2.0 ± 0.6ms, mean±S.D.) from the onset of single tooth tapping; (2) the wave forms of their unitary spike responses; and (3) the ability to follow faithfully trains of repetitive stimuli applied to the anterior superior alveolar nerve at rates of more than 100 Hz for 2 s. The responses of the identified primary mechanoreceptive neurons in the MeNV were tested for repetitive tapping and trapezoidal pressure to the ipsilateral upper incisor. The highest frequency of one-to-one following was observed in repetitive tapping at 100 Hz. All of the 27 tested neurons exhibited such very rapid adaptation as to show only on-off responses to trapezoidal pressures, and did not respond at all unless the pressures were applied more rapidly than 0.6 Newton/s (N/s). In most of these neurons, the number of evoked spikes was greater in on-responses than in off-responses, and the number and frequency of spikes were increased with an increase in the rate of pressure application. But in several neurons only one spike was triggered even when the pressures were applied at the rate of more than 83.1 N/s.     

Release of vasopressin by electrical stimulation of the intermediate portion of the nucleus of the tractus solitarius in rats with cervical spinal cordotomy and vagotomy

The cervical spinal cord abd vagi were severed in anesthetized and artificially ventilated. Monopolar electrical stimulation of the intermediate portion of the nucleus of the tractus (NTS) resulted in subtle increase in concentration of plasma vasopressin (pVP) and in arterial pressure. We suggest that electrical stimulation of the NTS in rats undergoing surch surgical preparation to observe the pressor response and/or increase in pVP, represents a rapid approach for screening the neurosecretory function of the central neural integration to release vasopressin.