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PubMed1986

Mapping of the normal distribution of substance P-like immunoreactivity in the spinal trigeminal nucleus of the cat.

Although a recent preliminary report indicated a pattern of substance P-like immunoreactivity within the spinal trigeminal nucleus that is similar to the projection sites for dental afferent fibers, details of this substance P distribution are lacking. Our purpose was to describe in cats the complete normal pattern of this immunoreactivity within each of the spinal trigeminal subnuclei. Special emphasis was given to the distribution of substance P-like immunoreactive axons and terminals located in the rostral subnucleus caudalis and the periobex region of subnucleus interpolaris, as these are regions shown to receive dental afferent fibers. Careful mapping in normal cats showed, within the resolution of the light microscope, a consistent pattern of distribution that included only a portion of the previously identified dental relay sites, but was somewhat broader in certain levels and more restricted in others. The results are compared with those provided by others from regions such as the dorsal horn and subnucleus caudalis of the spinal trigeminal nucleus. The findings also provide an anatomical basis for a recent physiologic report on specific cell types associated with dental nociceptive afferent fibers. This study also provides a baseline control for future investigations of possible changes in substance P-like immunoreactivity that follows various peripheral, including dental and central, lesions.

Animals↗
PubMed1993

Axon hillocks and initial segments in spinal trigeminal nucleus with emphasis on synapses including axo-axo-axonic contacts.

As a part of a continuing study of the feline spinal trigeminal nucleus, the fine structure and synaptic arrangements on the axon hillock and axon initial segment of neurons in this region are described here. Transmission electron microscopy has been used to characterize qualitatively the axon hillock and initial segment and associated synapses in pars interpolaris. Axon hillocks and initial segments are easily identified in continuity with somata or as isolated profiles in the neuropil, and they receive synaptic contacts: these we regard as axo-axonic. The presynaptic terminals contain either mainly round or mainly flattened synaptic vesicles and have Type I (asymmetric) or Type II (symmetric) thickenings respectively at their contacts with the axon hillock or initial segment. I report here also the unusual arrangement of three separate axons in a serial synaptic complex. Some of the round vesicle Type I contacts onto the axon hillock-initial segment region also receive Type II contacts from one or more flattened vesicle terminals, thus forming an axo-axo-axonic complex. These flattened vesicle terminals lack the usual features of a presynaptic dendrite. It has been shown that in this nucleus some round vesicle terminals, especially those postsynaptic to flattened vesicle terminals, are primary afferents from the periphery. Therefore the round vesicle terminal presynaptic to the axon hillock-initial segment region, some of which are included in the axo-axo-axonic complex may also be a primary afferent directly contacting the spike generator area of the relay neuron and under presynaptic control of a flattened vesicle synapse. The latter may possibly be an intrinsic contact. This strategic situation of round vesicle terminals and the axo-axo-axonic complex at the axon hillock or initial segment has major implications relevant to the overall output of these neurons.

Animals↗
PubMed1987

Opioid-mediated inhibition from the subnucleus caudalis of spinal trigeminal nucleus to the neurons in the subnucleus oralis.

The influence of enkephalin-containing neurons in the subnucleus caudalis of the spinal trigeminal nucleus (STN caudalis) on the subnucleus oralis of the STN (STN oralis) was examined using chloral hydrate-anesthetized rats. In the STN oralis, conditioning stimuli applied to the STN caudalis 10-50 ms preceding the test stimulus inhibited spikes produced by tooth pulp stimulation in type B interneuron, which was activated by orthodromic stimulation but not by thalamic stimulation, without affecting those of the relay neuron. When the type B interneurons were further classified into type B1 and type B2 neurons, which were characterized by the occurrence of the STN caudalis-induced inhibition with long and short latencies, respectively, microiontophoretically applied naloxone reduced the STN caudalis-induced inhibition of th orthodromic spikes of type B1 interneurons with little effects on type B2 interneuron. Furthermore, naloxone-reversible inhibition of tooth pulp-induced spikes of the type B1 interneurons were also observed during iontophoretic application of enkephalin. These results suggest that the type B1 interneurons in the STN oralis are inhibited by opioid peptides-containing neurons in the STN caudalis.

Action Potentials↗
PubMed1985

A morphometric study of the effects of maturation and aging on synaptic patterns in the spinal trigeminal nucleus of the cat.

Morphometric methods have been used to study the synaptic and terminal patterns in cat trigeminal nucleus, pars interpolaris, during development and aging. Ages 1, 3, 6, 11, 16, 21, 27, 110, 600 days and 8 and 11 years were studied. Both proportions and densities (number per unit area) of certain terminals and synapses showed significant changes with age. Axoaxonic synapses especially showed two major periods of increase (3-6 days and 21-27 days). The values of most parameters increased in the 21-27 day period to peak levels and then decreased gradually with age. The results indicate two separate critical synaptogenic periods of development and a loss of synaptic elements in aging. Factors contributing to these changes are discussed as is the potential for plasticity in the different afferents at each period.

Age Factors↗
PubMed1991

Selective involvement of the spinal trigeminal nucleus in the conditioned nictitating membrane reflex of the rabbit.

These experiments were performed to test the hypothesis that a region associated with the trigeminal nuclear complex is selectively involved in mediating the classically conditioned nictitating membrane reflex in the rabbit. Microinjections of Lidocaine were used to produce a temporary, localized block of neural activity following the conditioning of the reflex using a standard tone/air puff-paired stimulus paradigm. Data indicate that the injection of Lidocaine at the medial pars oralis/reticular formation junction results in a selective suppression of the conditioned reflex.

Animals↗
PubMed1992

Synaptic contacts established by primary sensory fibers innervating the teeth of rats: an ultrastructural study of the pars interpolaris of the spinal trigeminal nucleus.

Transganglionic degeneration was used in an electron microscopic study of afferent synaptic contacts in the dorsomedial region of the pars interpolaris of rats. In one experiment, the left inferior alveolar nerve was transected and in the other, partial pulpectomy of the first and second left lower molars was performed. Well defined degenerating terminals, almost completely occupied by round synaptic vesicle profiles were found in both ipsi and contralateral sides. In both experiments, approximately 70% of these terminals formed single asymmetric contacts with intermediate or distal dendritic segments. Fewer contacts were observed with proximal dendritic segments, dendritic spines, perikarya and other terminals. In addition, double and multiple synaptic contacts (synaptic glomeruli), accounting for 10% of the total, were also observed. Quantitative data regarding ultrastructural synaptic elements suggest that there is no preference for post-synaptic sites of fibers related to different sensory modalities such as pain, conveyed by dental fibers or other modalities, conveyed by the inferior alveolar nerve fibers.

Afferent Pathways↗
PubMed2004

Bidirectional modulation of windup by NMDA receptors in the rat spinal trigeminal nucleus.

Activation of afferent nociceptive pathways is subject to activity-dependent plasticity, which may manifest as windup, a progressive increase in the response of dorsal horn nociceptive neurons to repeated stimuli. At the cellular level, N-methyl-d-aspartate (NMDA) receptor activation by glutamate released from nociceptive C-afferent terminals is currently thought to generate windup. Most of the wide dynamic range nociceptive neurons that display windup, however, do not receive direct C-fibre input. It is thus unknown where the NMDA mechanisms for windup operate. Here, using the Sprague-Dawley rat trigeminal system as a model, we anatomically identify a subpopulation of interneurons that relay nociceptive information from the superficial dorsal horn where C-fibres terminate, to downstream wide dynamic range nociceptive neurons. Using in vivo electrophysiological recordings, we show that at the end of this pathway, windup was reduced (24 +/- 6%, n = 7) by the NMDA receptor antagonist AP-5 (2.0 fmol) and enhanced (62 +/- 19%, n = 12) by NMDA (1 nmol). In contrast, microinjections of AP-5 (1.0 fmol) within the superficial laminae increased windup (83 +/- 44%, n = 9), whereas NMDA dose dependently decreased windup (n = 19). These results indicate that NMDA receptor function at the segmental level depends on their precise location in nociceptive neural networks. While some NMDA receptors actually amplify pain information, the new evidence for NMDA dependent inhibition of windup we show here indicates that, simultaneously, others act in the opposite direction. Working together, the two mechanisms may provide a fine tuning of gain in pain.

Action Potentials↗
PubMed1996

Endogenous monoamines inhibit glutamate transmission in the spinal trigeminal nucleus of the guinea-pig.

1. With the use of whole-cell patch clamp recordings in slices of guinea-pig substantia gelatinosa (SG), we studied the serotonin (5-HT)- and noradrenaline (NA)-mediated inhibition of glutamate-mediated EPSCs evoked from primary afferent stimulation. 2. The frequency of spontaneous EPSPs was reduced by 5-HT and NA. 3. The inhibition of EPSCs caused by 5-HT was mediated by the 5-HT1D receptor subtype, since the 5-HT1D agonist, sumatriptan (1 microM), was effective. 4. NA and the alpha 2-agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14304), decreased the EPSCs and this inhibition was blocked by the alpha 2-antagonists, idazoxan (1 microM) and yohimbine (1 microM). 5. The 5-HT-releasing agent, fenfluramine (10 microM), and the Na-releasing agent, amphetamine (1 microM), also depressed EPSCs. Pretreatment of slices with the 5-HT-depleting agent, p-chloro-amphetamine (10 microM), attenuated the inhibition of fenfluramine but failed to antagonize the effects of exogenously applied 5-HT. 6. These in vitro results suggest that presynaptic inhibition of glutamate release from primary afferents can provide another mechanism to explain the antinociceptive effects of 5-HT and NA obtained in vivo.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2002

Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?

OBJECTIVE: To investigate trigeminal sensory processing in patients with migraine using a novel "nociception-specific" blink reflex. METHODS: Seventeen patients with unilateral migraine headache were studied within 6 hours of onset. Blink reflexes were elicited with a standard stimulating electrode (standard blink reflex) and concentric stimulating electrode (nociception-specific blink reflex) during the acute migraine attack, after treatment with IV lysine acetylsalicylate (1,000 mg) or oral zolmitriptan (5 mg) and interictally. RESULTS: After standard stimulation, no differences were detected for the R1 and R2 onset latencies and areas under the curve (AUC) between the different time points and the headache and nonheadache side. Nociception-specific stimulation revealed a shortening of R2 onset latencies (44.3 +/- 5.4 ms for headache side vs 48.9 +/- 5.8 ms for nonheadache side) during the acute migraine attack compared with the headache-free interval (49.8 +/- 5.3 vs 49.8 +/- 4.5 ms). The AUC of the R2 increased on the headache side by 680% and on the nonheadache side by 230% compared with the headache-free interval. Drug treatment parallel to pain relief increased the onset latencies (zolmitriptan: 48.0 +/- 8.2 ms for headache side vs 52.3 +/- 7.6 ms for nonheadache side; lysine acetylsalicylate: 48.0 +/- 5.0 ms for headache side vs 51.2 +/- 5.6 ms for nonheadache side) and reduced the AUC of R2 (zolmitriptan by 45% and lysine acetylsalicylate by 48%). CONCLUSION: The data suggest temporary sensitization of central trigeminal neurons during acute migraine attacks.

Acute Disease↗
PubMed1999

Projections from subnucleus oralis of the spinal trigeminal nucleus to contralateral thalamus via the relay of juxtatrigeminal nucleus and dorsomedial part of the principal sensory trigeminal nucleus in the rat.

Following injection of HRP into contralateral thalamus, retrogradely labeled cells were observed in principal sensory trigeminal nucleus (Vp) and an area of juxtatrigeminal nucleus (JX) formerly described by John and Tracey (1987). When PHA-L was delivered to dorsomedial part of the subnucleus oralis (Vodm), PHA-L labeled terminals were seen in dorsomedial part of the Vp (Vpdm) and in the JX region. Comparing the distribution of PHA-L labeled terminal field with that of HRP labeled JX neurons showed that the labeled terminals and neurons were overlapped closely in the JX. The distribution patterns of the labeled terminals and JX neurons were also the same: viewed on the coronal planes caudal-rostrally, both of the labelings began to appear at the levels where the facial nerve root was just broken. Rostrally, at middle levels of the motor trigeminal nucleus (Vmo), the labelings showed their typical view covering dorsal and ventral JX (dJX, vJX). The labelings disappeared at rostral poles of the Vmo and Vp. When injections of PHA-L into the Vodm and HRP into the contralateral thalamus was made in one rat, the contacts between Vodm projecting terminals labeled with PHA-L and HRP labeled trigemino-thalamic neurons were seen in the JX and also in the Vpdm. Then, electron microscopic (EM) study was done, injections of kainic acid into the Vodm and HRP into the contralateral thalamus was performed simultaneously. After EM embedding, the JX and Vpdm regions were selected, ultrathin sections were cut and observed with EM. In both areas, axo-somatic and axo-dendritic synapses were seen between degenerated boutons and HRP labeled somata or dendrites. Namely, the Vodm projecting terminals synapsed on trigemino-thalamic neurons in the JX and Vpdm. Anyway, axo-dendritic synapses was the main type of observed synapses. Thus, the present work demonstrated 1. the JX containing a group of trigemno-thalamic neurons was a target of special projections froin the Vodm; 2. The Vodm neurons projected to the contralateral thalamus through the relay of JX and Vpdm neurons.

Animals↗
PubMed1997

Ultrastructural study of NADPH-d positive neurons in laminae I and II of the rat caudal spinal trigeminal nucleus.

The present study investigated the ultrastructure of neurons in the caudal spinal trigeminal nucleus. These neurons which are believed to function as interneurons in the transmission of orofacial nonreflexive nociceptive information, measured 20 microns x 11 microns, and were nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) positive. The reaction product, formazan, was localized in the nuclear envelope, mitochondria, rough endoplasmic reticulum, and multivesicular bodies of these neurons. It was also localized in the membrane of the smooth endoplasmic reticulum at the axon terminal. The neurons were contacted by both axosomatic and axodendritic synapses formed by both NADPH-d positive and NADPH-d negative axon terminals. Two types of NADPH-d positive axon terminals could be recognized. The first was a large terminal containing many stained mitochondria and unstained small round agranular vesicles mixed with some slightly flattened ones. It formed asymmetrical axodendritic synapse. The second type of axon terminals contained pleomorphic synaptic vesicles and formed asymmetrical synapses upon both dendrites and soma. The sources of NADPH-d positive axon terminals were discussed. Most of the unstained axon terminals forming axosomatic and axodendritic synapses with stained cell bodies and dendrites contained flattened vesicles. In addition to the above, complicated synaptic configurations showing NADPH-d positive axoaxonic synapses in relation to NADPH-d negative dendritic spines were also seen in which a NADPH-d negative dendritic spine was completely contacted by a NADPH-d positive bouton which was in turn contacted by another NADPH-d positive bouton.

Animals↗
PubMed1999

FRAP-positive and capsaicin-sensitive terminals in the substantia gelatinosa of the mouse spinal trigeminal nucleus caudalis.

FRAP (fluoride-resistant acid phosphatase)-reactivity in the substantia gelatinosa of the mouse spinal trigeminal nucleus caudalis (STNC) was examined by light and electron microscopy. Degenerated figures of terminals caused by capsaicin were compared with the FRAP-positive terminals. Scalloped (fan-like) or indented, sinuous, slender, and cap-like figures with closely packed agranular synaptic vesicles of various sizes were common to both FRAP-positive and capsaicin-sensitive terminals. These terminals had glomerular or nonglomerular endings. Sometimes FRAP-positive and capsaicin-sensitive glomerular terminals made presynapses with surrounding dendrites. Frequently, both nonglomerular terminals were in direct contact with the neuronal soma. The terminal features of FRAP-positive and capsaicin-sensitive ones in the mouse STNC are the same as those seen in the superficial dorsal horn of the spinal cord. These findings suggest that some of the FRAP-positive terminals are capsaicin-sensitive, thereby indicating their nociceptive primary afferent.

Acid Phosphatase↗
PubMed1995

The colocalization of parvalbumin and calbindin-D28k with GABA in the subnucleus caudalis of the rat spinal trigeminal nucleus.

The colocalization of two calcium-binding proteins, parvalbumin (PV) and calbindin-D28k (CaB), which have been reported to be markers of specific subpopulations of neurons in the central nervous system, with the inhibitory amino acid neurotransmitter gamma-amino-butyric acid (GABA) was investigated in neurons of laminae I-IV of the subnucleus caudalis of the rat spinal trigeminal nucleus by using post-embedding immunocytochemical methods. Cells immunoreactive for PV, CaB, and GABA were found in all four laminae of the subnucleus caudalis. A substantial proportion of PV-immunoreactive perikarya were also stained for GABA in laminae II and III (44.8% and 39.8%, respectively). However, the majority of PV-containing neurons in laminae I and IV (100% and 86%, respectively), as well as CaB-immunoreactive cells in all four laminae (98.4%), were GABA-negative. These results show that, in contrast to higher brain centers, PV-, CaB-, and GABA-immunoreactive perikarya represent significantly different populations of neurons in the subnucleus caudalis of the rat. In the light of the present findings, the differences in the neurochemical properties of the subnucleus caudalis of the spinal trigeminal nucleus and the spinal dorsal horn are also discussed.

Animals↗
PubMed1980

In vitro release of 5-[3H]hydroxytryptamine from rat spinal trigeminal nucleus.

A potassium-evoked release of 5-[3H]hydroxytryptamine (5-HT), newly synthesized from [3H]tryptophan, was obtained from slices of the subnucleus caudalis of rat spinal trigeminal nucleus by means of an in vitro perfusion system. This release was dose-dependent and calcium-sensitive and quantitatively comparable to the 5-HT release in substantia nigra. The putative transmitter of the primary sensory afferents, substance P, stimulates the spontaneous 5-HT release, whereas another peptide, neurotensin, has no effect.

Animals↗
PubMed1997

Encoding of corneal input in two distinct regions of the spinal trigeminal nucleus in the rat: cutaneous receptive field properties, responses to thermal and chemical stimulation, modulation by diffuse noxious inhibitory controls, and projections to the parabrachial area.

To determine whether corneal input is processed similarly at rostral and caudal levels of the spinal trigeminal nucleus, the response properties of second-order neurons at the transition between trigeminal subnucleus interpolaris and subnucleus caudalis (Vi/Vc) and at the transition between subnucleus caudalis and the cervical spinal cord (Vc/C1) were compared. Extracellular single units were recorded in 68 Sprague-Dawley rats under chloralose or urethan/chloralose anesthesia. Neurons that responded to electrical stimulation of the cornea at the Vi/Vc transition region (n = 61) and at laminae I/II of the Vc/C1 transition region (n = 33) were classified regarding 1) corneal mechanical threshold; 2) cutaneous mechanoreceptive field, if present; 3) electrical input characteristics (A and/or C fiber); 4) response to thermal stimulation; 5) response to the small-fiber excitant, mustard oil (MO), applied to the cornea; 6) diffuse noxious inhibitory controls (DNIC); and 7) projection status to the contralateral parabrachial area (PBA). On the basis of cutaneous receptive field properties, neurons were classified as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), nociceptive specific (NS), or deep nociceptive (D). All neurons recorded at the Vc/C1 transition region were either WDR (n = 19) or NS (n = 14). In contrast, 54% of the Vi/Vc neurons had no cutaneous receptive field. Of those Vi/Vc neurons that had a cutaneous receptive field, 57% were LTM, 25% were WDR, and 18% were D. All Vc/ C1 neurons responded to noxious thermal and MO stimulation. Only 22 of 47 and 13 of 19 Vi/Vc corneal units responded to thermal or MO stimulation, respectively. At the Vc/C1 transition region, 12 of 17 neurons demonstrated DNIC, whereas at the Vi/Vc transition region, DNIC was present in only 4 of 26 neurons. Of 15 Vc/C1 corneal units, 12 could be antidromically activated from the contralateral PBA (average latency 6.29 ms, range 1.8-26 ms). None of 22 Vi/Vc corneal units tested could be antidromically activated from the PBA. These findings suggest that neurons in laminae I/II at the Vc/C1 transition and at the Vi/Vc transition process corneal input differently. Neurons in laminae I/II at the Vc/C1 transition process corneal afferent input consistent with that from other orofacial regions. Corneal-responsive neurons at the Vi/Vc transition region may be important in motor reflexes or in recruitment of descending antinociceptive controls.

Anesthetics↗