Substance P-like immunoreactive fibres in the ventromedial mesencephalic tegmentum of rat

The distribution and morphology of the substance P-like immunoreactive (SP-IR) fibres and terminals in the rat ventromedial mesencephalic tegmentum (VMT) were studied using qualitative and quantitative immunohistochemical methods at light and electron microscopic levels. All five component nuclei of the VMT were examined and the size, number and density of immunoreactive terminals determined. The SP-IR fibres were distributed heterogeneously within the VMT. Under the electron microscope, SP-IR axon terminals contained both clear and dense-cored vesicles and made both symmetrical and asymmetrical synapses. The ultrastructure of the SP-IR terminals appeared to differ between nuclei. Small, clear vesicle terminals made symmetrical synaptic junctions with small calibre dendrites in the paranigral nucleus while large, clear and dense-cored vesicle terminals made asymmetrical junctions with somata and large calibre dendrites in the interfascicular nucleus. Quantitative differences between the VMT nuclei were also seen in the density of SP-IR terminals, the paranigral nucleus contained the highest density and the rostral linear nucleus the lowest. A comparison between the number of SP-IR terminals and the total number of axon terminals in the VMT reveals that the majority of all terminals in the paranigral nucleus were SP-IR, as well as the majority of axosomatic synapses in the interfascicular nucleus. These regional differences in the SP-IR innervation suggest that substance P and related peptides may perform several specific functions within the VMT and therefore have a more variable influence on this region than was previously thought.     

Distribution of substance P-like immunoreactivity in the lower brainstem of the human fetus: An immunohistochemical study

The regional distribution of substance P-like immunoreactive (SPI) structures in the lower brainstem of the human fetus was investigated using the indirect immunoflourescence technique. SPI cells were found in a number of areas including the inferior colliculus, central gray matter of the midbrain, n. laterodorsalis tegmenti, midbrain and medullary reticular formation, n. vestibularis inferior, and n. prepositus hypoglossi. An extensive network of SPI fibers of varying densities were identified throughout the lower brainstem.     

Substance P-like immunoreactivity and somatostatin-like immunoreactivity in the ventricular fluid of patients with chronic pain syndromes

Summary Substance P-like and somatostatin-like immunoreactivities (SPLI and SLI) were determined in ventricular fluid of patients with chronic pain syndromes and in a comparison group with multiple sclerosis, essential tremor, epilepsy and postanoxic myoclonus. Concentrations of SPLI and SLI were non-significantly decreased by 40% and 33% in chronic pain patients as compared with control patients without pain. There were no differences apparent between subgroups of pain patients (deaferentation pain, neoplasia-induced pain, thalamic pain). High pressure liquid chromatography combined with radioimmunoassay showed marked heterogeneity of SPLI and SLI.     

Development of substance P-immunoreactive neurons in cranial sensory ganglia of the rat

Substance P-like immunoreactivity has been observed in fetal and adult cranial sensory ganglia. It first appears at day 16 of gestation in sensory neurons of trigeminal, superior-jugular, petrous and nodose ganglia, as well as in the autonomic myenteric plexus, and at day 17 in cervical dorsal root ganglion cells. Substance P immunoreactivity can be visualized much earlier (day 12) in the central nervous system. The ganglionic immunoreactivity subsequently increases during fetal life but drops at birth. The reactive material is first diffuse, then slowly becomes granular, and is mostly concentrated in coarse perinuclear inclusions in adult sensory neurons. Most substance P-positive neurons in trigeminal and superior-jugular ganglia are small, but medium-sized and large positive neurons are also observed in the trigeminal, petrous and nodose ganglia.Our observations give a precise picture of the development of substance P immunoreactivity in sensory neurons and are in general agreement with previous reports on some fetal and adult rat sensory ganglia. They indicate that in the rat, maturation of peripheral substance P-containing sensory neurons is slower than that of central substance P neurons or equivalent sensory neurons in other species. The examination of fetal material allows the observation of numerous immunoreactive sensory neurons which cannot be visualized after birth. We hypothesize a possible different embryonic origin (neural crest or placodal) for small nociceptive and larger substance P-containing neurons in rat cranial sensory ganglia.     

Substance P-like immunoreactivity in plasma of psychotic patients and effects of neuroleptics and electroconvulsive therapy

Radioimmunoassay of substance P (SP)-like reactivity, using N^α-tyrosyl-SP, was performed in plasma of psychotic patients. Schizophrenic patients under neuroleptic medication over 1 year, and those patients with organic brain disease showed a significant increase in immunoreactivity. The immunoreactivity in unmedicated schizophrenic patients just before treatment and in depressed patients, both bipolar and major, did not differ significantly from that of controls. The immunoreactivity in unmedicated schizophrenics was followed after medication for a maximum of 5 months. The reactivity decreased in five cases, and increased in three cases. No definite pattern could be discerned between changes in the immunoreactivity, the type of medication administered, and the resultant response to the therapy. Chlorpromazine injection caused no definite acute effect on the plasma level of SP-like immunoreactivity for 120 minutes. Electroconvulsive therapy increased the plasma level of SP-like immunoreactivity for 90 minutes in a male schizophrenic patient.     

Prenatal ontogeny of substance P-like immunoreactivity in the parabrachial nucleus of the human fetus — an immunocytochemical study

Using an immunocytochemical method, the prenatal ontogeny of substance P-like immunoreactivity (SP-LI) was demonstrated in the parabrachial nucleus (PB) of human fetus, fetal age (menstruation age) 11.5 to 40 weeks. The time of initial appearance of SP-LI in the human brainstem PB was between fetal age 11.5 weeks and 16 weeks. While the fetus grew, the density of SP-LI fibers and terminals in the human fetus brainstem PB increased constantly from fetal age 16 weeks to 40 weeks. These findings indicate that substance P (SP) might play an important role in the human parabrachial nucleus development and in its functional establishment during the prenatal period.     

Substance P-like immunoreactivity in human sympathetic ganglia

The substantia nigra (SN) of the cat was shown, by the anterograde and retrograde horseradish peroxidase methods, to contain neurons which send their axons to the caudomedial portions of the suprageniculate nucleus and/or lateroposterior nucleus of the thalamus; these neurons were located in the restricted region in the lateral part of the SN, which corresponds to the pars lateralis of the SN.     

An immunohistochemical study of methionine-enkephalin-Arg-Gly-Leu-like immunoreactivity-containing neurons in the parasympathetic preganglionic regions of the rat spinal cord

The localization of the methionine-enkephalin-Arg⁶-Gly⁷-Leu⁸ (Met-Enk-Arg-Gly-Leu)-like immunoreactivity-containing neurons in the rat lumbosacral spinal cord was immunohistochemically examined by an antiserum very specific to Met-Enk-Arg-Gly-Leu. The immunoreactive neurons occupied the positions corresponding to the parasympathetic preganglionic nuclei determined by the previous horseradish peroxidase (HRP)-tracing experiments. The present study suggests that the parasympathetic preganglionic neurons in the rat lumbosacral spinal cord produce preproenkephalin A and its related peptides.     

Spinoparabrachial tract neurons showing substance P receptor-like immunoreactivity in the lumbar spinal cord of the rat

By using substance P receptor (SPR) immunofluorescence histochemistry combined with fluorescent retrograde labeling, SPR-like immunoreactive (SPR-LI) neurons sending their axons to the lateral parabrachial region were observed in the lumbar spinal cord of the rat. After injection of Fluoro-Gold into lateral parabrachial region, retrogradely labeled neurons with SPR-LI were seen frequently in lamina I and the lateral spinal nucleus, and occasionally in laminae IV and V, with a predominantly contralateral distribution. Some of these neurons, especially those in lamina I, may convey nociceptive information to the lateral parabrachial region.     

Evidence for the presence of substance P-like immunoreactivity in the human cerebellum

Preliminary results on the localization of substance P-like immunoreactivity in the human cerebellum are presented. Cerebella from newborn and adult subjects were examined. While only sporadic positive fibres were detected in the adult tissue, the immunoreactive material appeared more abundant in the cerebella from newborn subjects. Varicose and non-varicose fibres and dot-like nerve terminals were present with different density in various regions. The paucity of immunoreactive perikarya suggests that most of the cerebellar substance P-like immunoreactive material has an extrinsic origin.     

Distribution of substance P-like immunoreactivity in guinea pig central nervous system

The distribution of substance P-like immunoreactivity (SP-LI) in the guinea pig brain has been studied by immunohistochemistry and the results compared with the distribution in similar regions in the rat brain. In both species, dense SP-LI staining was found in the median eminence, arcuate hypothalamic nucleus, substantia nigra, dorsal raphe and dorsal tegmental nuclei, nucleus of the solitary tract, substantia gelatinosa of the spinal trigeminal nucleus, and spinal cord. Less dense staining was found in the caudate putamen, globus pallidus, nucleus accumbens, habenula, hypothalamic areas, and central grey. SP-LI cell bodies were found in areas previously described for the rat brain including several hypothalamic areas, limbic areas, central grey, and dorsal raphe and solitary tract nuclei. The major difference between the two species was found in the cortex and hippocampus. The guinea pig cortex contained many more SP-LI cells and fibres, distributed in layers II-VI, than the rat cortex. The guinea pig hippocampus contained marked staining, particularly in the pyramidal cell layer of CA1-3 fields of Ammon's horn and in the granular layer of the dentate gyrus, and SP-LI cells in the hilus of the dentate gyrus, whereas rat hippocampus contained few cells and no regions of dense staining. It is concluded that because the guinea pig brain has an extensive distribution of SP-LI in the cortex and hippocampus it resembles the primate brain more closely than does the rat brain.     

Prenatal ontogeny of substance P-like immunoreactivity in the trigeminal spinal caudal subnucleus of the human fetus — an immunocytochemical study

Using an immunocytochemical method, the prenatal ontogeny of substance P-like immunoreactivity (SP-LI) was demonstrated in the trigeminal spinal caudal subnucleus (TSCS) of human fetus, fetal age (menstruation age) 11.5–40 weeks. The time of initial appearance of SP-LI in the human brainstem TSCS was between the fetal age 11.5 weeks and 16 weeks. While the fetus grew, the density of SPLI fibers and terminals in the human fetus brainstem TSCS increased constantly from fetal age 16 weeks to 40 weeks. These findings indicated that substance P (SP) might play an important role in the human trigeminal nerve system development and in its functional establishment during the prenatal period.     

Substance P-like immunoreactivity in human prenatal hippocampal formation

Presence and localization of substance P-like immunoreactive neuronal structures in human hippocampal formation during prenatal stages of ontogenesis are reported. In fetuses at 16 and 17 weeks of gestation immunoreactivity is very scarce and represented only by sporadic fibres in Ammon's horn and the entorhinal area. In specimens at 25 and 26 weeks of gestation, more or less intensely labelled perikarya of different morphology are easily detectable in deep layers of Ammon's horn and the hilus of fascia dentata. Immunoreactive beaded fibres are also present at this stage. The possibility of the existence of a substance P-containing extrinsic projection to Ammon's horn is pointed out.     

Substance P and neurokinin A mediate sensory synaptic transmission in young rat dorsal horn neurons

Spinal nociceptive transmission is mediated by glutamate and neuropeptides such as substance P (SP) and neurokinin A (NKA). The neuropeptide-mediated excitatory postsynaptic potentials (EPSPs) had a slow onset and long duration. Here, we demonstrate SP- and NKA-mediated excitatory postsynaptic currents (EPSCs) in dorsal horn neurons of young rats using whole-cell patch-clamp recording techniques. After complete blockade of glutamate receptor-mediated currents, we observed a small residual EPSC. The residual EPSCs exhibited temporal summation in response to a train of stimulation (six pulses delivered at 10-50 Hz). High intensity stimulation (the same or greater than the stimulation threshold for nociceptive fibers in vivo) was required for evoking these summated EPSCs. Summated EPSCs were attenuated or abolished by capsaicin pretreatment, which depletes SP and NKA from presynaptic terminals; SP and NKA pretreatment; NK(1) or NK(2) receptor antagonists; and inhibition of postsynaptic G proteins. EPSCs were neither blocked by a metabotropic glutamate receptor antagonist nor a gamma-aminobutyric acid(B) receptor antagonist. The summated EPSCs were also sensitive to voltage-gated calcium channel antagonists or mu-opioid receptor activation by DAMGO. The present study provides electrophysiological evidence that suggests the possible contribution of SP and NKA to sensory synaptic transmission between primary afferent fibers and dorsal horn neurons.     

Substance P-like immunoreactive nerve fibers of the human laryngeal mucosa--preliminary report

Substance P (SP) is considered a primary sensory transmitter and is widely distributed within the autonomic nervous system. This study is concerned with the distribution of SP-like immunoreactive nerve fibers in the human larynx. Individual SP-like immunoreactive nerve fibers were detected in the subepithelial connective tissue of the laryngeal mucosa, in the ventricular and subglottic glandular regions and in a few nervous ganglia in the deep connective tissue. No intraepithelial SP-like immunoreactive fibers were present in our material.

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Sommario La sostanza P è considerata essere un importante neurotrasmettitore sensoriale, ampiamente distribuito all'interno del sistema nervoso autonomo. Il presente studio è volto ad individuare la presenza di fibre nervose immunoreattive per la sostanza P, o per peptidi ad essa correlati, nel contesto della laringe umana. Si sono repertate singole fibre immunoreattive per la sostanza P a livello del connettivo subepiteliale della mucosa laringea, delle regioni ghiandolari ventricolare e sottoglottica e in alcuni rari gangli presenti nel tessuto connettivale profondo. Nel materiale in esame non si sono repertate fibre intraepiteliali.

     

Quinolinic and kainic acids can enhance calcitonin gene-related peptide-like immunoreactivity in striatal neurons with substance P-like immunoreactivity

Quinolinic or kainic acid, when injected into the cat striatum, caused neurodegenerative changes in striatal neurons. In parallel with these changes, however, calcitonin gene-related peptide-like immunoreactivity became visible in perikarya of many striatal neurons which were distributed around the lesions produced by the quinolinic or kainic acid injections. The vast majority of these lesion-spared neurons showing calcitonin gene-related peptide-like immunoreactivity were striatal neurons with substance P-like immunoreactivity.     

Chemical characterization of substance P-like immunoreactivity in primary afferent neurones

Substance P-like immunoreactivity (SPLI) in rat dorsal root ganglia and dorsal spinal cord was characterized by high-performance liquid chromatography followed by radioimmunoassay. In spinal cord and ganglia, respectively, 87% and 64% of SPLI eluted with authentic SP. The remainder of the SPLI in ganglia eluted as a single peak which did not represent the sulphoxide of SP or any of its C-terminal fragments.     

Substance P and serotonin immunoreactivity in the rat inferior olive

The present study analyzes in detail the distribution of substance P and serotonin immunoreactivity in the inferior olivary complex of the rat using the indirect antibody peroxidase-antiperoxidase technique. The entire dorsal accessory olive contains an abundance of substance P fibers and varicosities. In addition, the dorsal cap of Kooy, nucleus Beta, parts b and c of the medial accessory olive, and the dorsomedial cell column contain numerous substance P immunoreactive elements. Fibers and varicosities positive for serotonin are present throughout the entire dorsal accessory olive. In addition, the rostral medial accessory olive contains an abundance of serotonin immunostaining. Scattered serotonin immunoreactive elements are present in the principal olive in particular in the area immediately subjacent to the lateral aspect of the dorsal accessory olive. Only scant serotonin immunolabeling is present in the dorsal cap of Kooy, nucleus Beta and the dorsomedial cell column. Speculations on possible functional roles of these two putative neurotransmitters are presented.     

Reduced substance P-like immunoreactivity in hereditary sensory neuropathy of Pointer dogs

Summary Two unrelated Pointer dogs, each from a breeding of normal parents which produced three affected pups in a litter of nine, began to bite their paws at 3 and 5 months of age. Insensitivity to painful stimuli was marked in the distal parts of the limbs and receded proximally. The affected dogs were euthanatized at 5 and 20 months because of acral mutilation and infection. Changes affecting the primary sensory neurons included: small spinal ganglia with reduced numbers of cell bodies, degeneration of unmyelinated and myelinated fibers in dorsal roots and peripheral nerves, and reduced fiber density in the dorsolateral fasciculus (dlf).Since nociceptive loss was the salient deficit in a neuropathy affecting primary sensory neurons, immunohistochemical studies focused on substance P, the undecapeptide imputed to mediate nociception at the first synapse in the spinal cord and brain. The localization and density of substance P-like (SPL) immunoreactivity was studied in three control dogs and the two Pointers by the indirect antibody peroxidase-antiperoxidase method. The spinal intumescences of the control dogs contained dense SPL-immuno-reactivity in fibers of the dlf and the superficial laminae of the dorsal horn (i.e., laminae I, II, and the dorsal part of III). Immunoreactive fascicles on the lateral aspect of the dorsal horn and in the reticular process sent contributions medially to a plexiform fiber arrangement in lamina V. Medially, SPL-immunoreactive fibers were more loosely arranged in the internal third of laminae VI and VII and in lamina X. In the Pointers, the loss of primary sensory neurons was associated with notable reduction of SPL staining in the dlf and superficial laminae of the dorsal horn. In the lumbar intumescence of the older Pointer greater preservation of SPL staining in the lateral third of laminae I and II was consistent with somatotopic termination of trunkal afferents in this region.In both Pointers there was no detectable decrease in trigeminal sensitivity and the SPL immunoreactivity in the spinal nucleus of the trigeminal nerve of the younger Pointer and the corresponding control dog appeared equivalent. In the older Pointer, however, the immunoreactivity in this nucleus was decreased relative to the control. This decrease and appearance of scattered fiber degeneration in the dorsal columns of the mature Pointer suggested that fiber degeneration progresses slowly with age to include sensory systems not affected in early postnatal life.The findings in the Pointers were compared with those made in immunohistochemical studies of SP in familial dysautonomia and the mutilated foot rat.Supported in part by a grant from the Rockland County Kennel Club     

The co-occurrence of substance P-like immunoreactivity and dynorphin-like immunoreactivity in striatopallidal and striatonigral projection neurons in birds and reptiles

Using an immunofluorescence procedure that allows the simultaneous labeling of tissue for two different antigens, substance P-like immunoreactivity (SPLI) and dynorphin-like immunoreactivity (DLI) were observed to co-occur extensively in striatal neurons of the avian and reptilian basal ganglia and in fibers and terminals in the projection targets of the avian and reptilian striata. Thus, SPLI and DLI apparently co-occur extensively in striatopallidal and striatonigral projection neurons of the avian and reptilian basal ganglia. Since basal ganglia organization is fundamentally similar among amniotes, the present results suggest that SPLI and DLI may also co-occur extensively in striatal neurons in mammals.