Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P- and calcitonin gene-related peptide-like immunoreactivities (SP-LI and CGRP-LI, respectively) were measured in superfusates of either superior sagittal sinus and transverse sinuses and attached dura mater or dura mater alone of guinea pig. Exposure of cerebral venous sinuses to capsaicin (1 microM) evoked the release of both SP-LI and CGRP-LI, which was no longer observed upon second challenge with the drug. Neuropeptide release was induced by 80 mM K+ either at the first or second administration. Bradykinin (10 microM) increased the outflow of CGRP-LI, but not of SP-LI, from cerebral venous sinuses. In vitro capsaicin pretreatment (10 microM) or incubation with 10 microM indomethacin completely abolished the bradykinin-evoked CGRP-LI release. Capsaicin (1 microM) failed to evoke release from dura mater without major intracranial venous vessels. Sensory neuropeptide released from the cerebral venous sinuses may take part in certain symptoms, such as vasodilatation and inflammation accompanying the pain of the migraine attack. Bradykinin, putatively via prostanoid generation, may participate in this event.
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PMID:Release of sensory neuropeptides from dural venous sinuses of guinea pig. 169 Oct 44

The presence of enkephalin and substance P-positive neurons and fibers were studied by immunohistochemistry (peroxidase-antiperoxidase or avidin-biotin-peroxidase complex methods) in 26 human fetuses ranging from 11 weeks of gestation to 40 weeks of gestation. Enkephalin-positive neurons were localized in the commissural, medial and intermediate subnuclei as early as 11-12 weeks' gestation. Positive enkephalin fibers were localized around 12 weeks' gestation and in many subnuclei, notably the medial, commissural, intermediate, ventrolateral, ventral and dorsolateral subnuclei. Substance P-positive neurons were localized in the commissural and medial subnuclei around gestation age 13 weeks. Positive substance P fibers appeared even earlier, around 11 weeks of gestation in many subnuclei, notably the medial, intermediate, ventral, ventrolateral and dorsolateral subnuclei. Increase in both enkephalin- and substance P-positive fibers was evident in the later stages of development (e.g. around 26 weeks of gestation). The importance of the early appearance of enkephalin and substance P neurons and fibers of the pain pathways in the major subnuclei connecting with the cardiovascular, gastrointestinal and respiratory functions in the human has to be stressed.
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PMID:Development and localization of enkephalin and substance P in the nucleus of tractus solitarius in the medulla oblongata of human fetuses. 169 13

Substance P (SP) found in the dorsal horn of the spinal cord has been proposed as a mediator of nociception. Formalin injected into the hind paw of a rat as a nociceptive stimulus has been shown to increase the amount of immunoreactive SP in the dorsal horn, perhaps by decreasing SP release from primary afferent neurons. These SP changes may be due to the actions of endogenous opiates which can block SP release from primary afferent neurons. In order to determine the time course of SP changes in the dorsal horn and their modulation by naloxone, anesthetized rats pretreated subcutaneously with naloxone or saline were injected in the right hind paw with 0.4 ml of either saline or 5% formalin. After various time intervals, the animals were perfused and the lumbar enlargement of the spinal cord removed. Immunohistochemical staining and manual photometry were used to quantitate SP-like immunoreactivity (SPLI) in the dorsal horn. The results show that saline injection produced an increase in SPLI lasting 20 min, while formalin produced a biphasic effect with early (0-20 min) and late (20-60 min) increases in SPLI. Naloxone pretreatment 30 min prior to hind paw injection partially blocked the initial SPLI increase due to saline or formalin. However, this was not the case if naloxone was injected 2 min following hind paw injection. The formalin-induced late SPLI increase was blocked by naloxone only if it was administered prior to the formalin. This blockade of SPLI increases in the dorsal horn by naloxone implies that endogenous opioid systems play a role in the control of SP levels in the dorsal horn during nociception.
Pain 1990 Apr
PMID:Time course of the alteration in dorsal horn substance P levels following formalin: blockade by naloxone. 169 64

Characterization of the distribution of the peptide-degrading enzyme neutral endopeptidase-24.11 (E.C. 3.4.24.11; NEP; enkephalinase) in the rat brainstem was examined by means of a unique fluorescent histochemical method. Enzyme staining was completely blocked by three potent NEP inhibitors (thiorphan, phosphoramidon, and JHF-26) at a concentration of 50 nM, supporting the specificity of this method to visualize sites of NEP activity selectively. At all levels of the brainstem, NEP was localized to cell bodies, cell processes or terminal-like fields and was localized to more than 90 distinct nuclei or subnuclei. In the mesencephalon these included the central gray, cuneiform n., dorsal and lateral tegmental n., inferior colliculus, interpeduncular n., lateral and medial geniculate n., central linear raphe n., mesencephalic n. of the trigeminal nerve, mammillary nuclei, occulomotor n., red n., superior colliculus, ventral n. of the lateral lemniscus, substantia nigra-ventral tegmental area, and the zona incerta. In the pons, NEP staining was restricted to fewer regions or nuclei, including the dorsal and ventral cochlear n., facial n., motor trigeminal n., principal sensory trigeminal n., parabrachial nuclei, pontine n., the oral and caudal pontine reticular n., pontine olivary nuclei, several pontine tegmental nuclei, pontine raphe nuclei, and the trapezoid n. In the cerebellum, staining was localized largely to the granule cell layer of the cerebellar cortex. Scattered staining was observed in the molecular cell layer. The medulla contained extensive NEP staining localized to nuclei that included the ambiguous n., dorsal motor n. of the vagus, hypoglossal n., inferior olivary n., prepositus hypoglossus n., solitary tract n., nuclei of the spinal tract of the trigeminal n., and the lateral, medial, and superior vestibular nuclei. Nuclei of the medullary reticular formation that were also richly stained for NEP included the raphe magnus n., raphe obscurus n., raphe pallidus n., dorsal, lateral, and ventral reticular nuclei of the medulla, and the gigantocellular, lateral paragigantocellular, linear, paramedian and parvicellular reticular nuclei. The widespread distribution of NEP in the brainstem suggests the existence of a number of functional systems, including the pathways involved in the mechanisms of pain and analgesia, which are potential targets of NEP inhibitors. In most regions, the distribution of NEP closely overlapped with that reported for the enkephalins, and showed a more restricted overlap with the reported distribution of substance P.
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PMID:Fluorescent histochemical localization of neutral endopeptidase-24.11 (enkephalinase) in the rat brainstem. 169 88

We have previously shown the depletion of cutaneous calcitonin gene-related peptide (CGRP)- and substance P-containing nerves in human leprosy. The aims of this study were to investigate the temporal effects of leprosy on nerves in skin and spinal cord. Tissues were taken from nude mice, 6 and 12 months after inoculation of Mycobacterium leprae into the hind footpads, and from age-matched controls. Sections were immunostained with antisera to substance P or CGRP. After 6 months of infection, substance P- and CGRP-immunoreactive nerves were reduced in skin from all body areas; by 12 months, the reduction was substantially greater. In the spinal cord, sensory fibres immunoreactive for substance P had decreased compared with controls at 6 and 12 months [by 60 per cent (0.022 mm2) and 80 per cent (0.048 mm2), respectively, P less than 0.001], as with CGRP [30 per cent (0.018 mm2) (P less than 0.02) and 40 per cent (0.028 mm2) (P less than 0.01), respectively]. CGRP immunoreactivity was completely absent in motor neurones after 12 months of infection. Loss of CGRP- and substance P-immunoreactive fibres in skin and spinal cord, and CGRP in motor neurones is in accord with impaired pain sensation and muscle weakness in leprosy.
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PMID:Time-related decrease of substance P and CGRP in central and peripheral projections of sensory neurones in Mycobacterium leprae infected nude mice: a model for lepromatous leprosy in man. 169 40

Twenty-three perioperative tissue samples from lumbar disc operations on 11 patients were studied immunohistochemically using the sensitive avidin-biotin-peroxidase complex (ABC) method and specific heterologous antisera for the presence of neurofilament-positive neural elements containing nociceptive neuropeptides substance P (SP) and/or calcitonin gene-related peptide (CGRP). Histologically, neural elements were especially abundant in the posterior longitudinal ligament, there being also a few demonstrable nerves in the peripheral anulus fibrosus. These nerves often showed a co-localization of cytoskeletal neurofilaments together with SP and/or CGRP immunoreactivity. It is suggested that pressure and chemical irritation of nociceptive nerves dependent on degenerated discs excite sensory neural elements, especially in the posterior longitudinal ligament and possibly also in the peripheral parts of the anulus fibrosus, while the disc itself, at least if not penetrated by vascular granular tissue, is painless and neuroanatomically lacks a structural basis for pain perception.
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PMID:Neuroimmunohistochemical analysis of peridiscal nociceptive neural elements. 169 99

The sensory innervation of the rabbit urinary bladder was studied using local application of the specific sensory neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). This agent has its major effect by damaging small diameter unmyelinated sensory nerves. The drug produced a 51% reduction in the bladder content of the neuropeptide substance P. It therefore appears that a substantial proportion of the bladder's content of the peptide is to be found in capsaicin-sensitive sensory nerves. Cystometrograms carried out before and after treatment with capsaicin were similar; this suggests that capsaicin-sensitive sensory nerves may not be of importance in the afferent limb of the micturition reflex. In vitro muscle strip studies demonstrated a small reduction in the sensitivity of the detrusor muscle to electrical stimulation of its intramural nerves. It is possible that in vitro intramural nerve stimulation leads to release of neurotransmitters from sensory as well as motor nerves. It is proposed that small diameter sensory nerves in the bladder wall may have a role in the transmission of the sensation of pain and in the triggering of inflammatory reactions rather than forming the afferent limb of the micturition reflex.
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PMID:Effect of capsaicin on the rabbit urinary bladder. What is the function of sensory nerves that contain substance P? 169 3

This review summarized some articles on the effect of the septal area in acupuncture analgesia. The data showed that the pain threshold of animal was increased when septal area was stimulated by electro-acupuncture, and that electrical stimulation of septal area had a marked inhibitory effect on the pain discharges of cells in parafascicular nucleus of thalamus, lateral habenular nucleus, periaqueductal gray and dorsal raphe nucleus. The septal area play an important role in acupuncture analgesia. The majority of the cholinergic neurons in septal area are located in nucleus of the vertical limb of the diagonal band (VDB); gamma-aminobutyric acid of septal area is mainly found in the diagonal band nucleus(td); Dopamine is present in high levels in td and lateral septal nucleus(S1) of septal area; The S1 contain high densities enkephalin-containing neuronal cell bodies and terminals; In addition, substance P and norepinephrine are also high levels in the septal area. These substance above-mentioned have a relations with acupuncture analgesia of septal area. A large number of serotonin-containing neurons are found in the raphe nuclei. The serotonin play an important role in acupuncture analgesia. The serotonin-containing neurons in dorsal raphe nucleus project to S1. The fiber connections of the raphe nuclei with the td are reciprocation. The periaqueductal gray is a important structure on pain modulation. It projects to septal area and receives the fibers from S1. A number of adrenergic neurons are located within the locus coeruleus. The locus coeruleus participate pain modulation and acupuncture analgesia. The neuro-anatomy study demonstrated that locus coeruleus projects to septal area.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of the septal area in acupuncture analgesia]. 169 24

The influence of nociceptive peripheral input on the response characteristics of spinal interneurons may result in long-term alterations of interneuronal excitability and modify their responses to subsequent stimuli. Such neuromodulation has been found to result in physiological changes including hyperalgesia, lowering of pain thresholds, expansion of receptive fields and changes in response behaviors of muscles. These types of alterations may contribute to clinically significant findings including muscle spasm, hypomobility, edema, chronic pain, recurrences in areas of previous injury and resistance to treatment. This article reviews studies concerning plasticity of response behaviors of interneurons including habituation, spinal learning, spinal fixation, neuromodulation and the effects of substance P. Potential clinical and chiropractic application are discussed and a brief review of clinically relevant studies of chiropractic adjustments are cited.
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PMID:Spinal learning: central modulation of pain processing and long-term alteration of interneuronal excitability as a result of nociceptive peripheral input. 169 16

Thermal injury to one hind limb of rats was induced by immersion into water at 62 degrees C. Both a mild (15 s) or severe (30 s) lesion caused inflammation of the limb when observed 24 h later; but at this time the animals used the injured limb when they walked. Animals with a severe lesion of the injured limb subsequently withdrew it from use when walking. Limb withdrawal did not occur following a mild lesion. At 24 h following the lesion, lumbar spinal cord levels of [Met]enkephalin, as measured by radioimmunoassay, were elevated (70%) bilaterally in both hemisegments, ipsi- and contralateral to the lesion. At seven days following either mild or severe hind limb lesion [Met]enkephalin levels were elevated only in the ipsilateral lumbar hemisegment. At that time no changes in thoracic [Met]enkephalin levels were observed. Substance P levels were decreased (20-25%) bilaterally in the lumbar cord 24 h following a severe limb lesion, but no change was observed at seven days in any cord segment following a mild or severe lesion. Changes in spinal cord [Met]enkephalin content occur in response to thermal injury to one hind limb. However, the changes do not appear to be related to the withdrawal of the damaged limb from use following a severe lesion. Peptide changes in the spinal cord may reflect pain or injury to the damaged limb following a thermal lesion. In contrast, limb withdrawal may be a physiological rest mechanism related to altered basal ganglia peptide function.
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PMID:Increased [Met]enkephalin and decreased substance P in spinal cord following thermal injury to one limb. 170 Mar 32


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