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)

The response of sensory nerve fibres to inflammation in young adult rat molars has recently been shown to include increases in nerve sprouting and neuropeptide content. The objective was to evaluate neural responses to class V dental preparations in molars of old (1-2 yr) as compared with young adult rats (3-4 months). Tissues were investigated immunocytochemically 4 days post-injury for the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P. Quantitative image analysis of the material demonstrated that more immunoreactivity was present for CGRP than for substance P in intact control teeth for each age group. Four days after injury, both immunoreactivities were increased in pulp adjacent to the injury in both young and old teeth. The increase depended on at least three factors: (1) enhanced immunoreactivity of the nerve fibres; (2) increased terminal nerve sprouts near the injury and (3) elevated peptide content of the pulp tissue. Although the incidence of CGRP- and substance P-immunoreactive nerve fibres had decreased in older teeth, the proportional increases in both neuropeptides near the injury were greater in old than in young teeth, owing to a reduction in pulpal volume during ageing. Pulpal tissue was also immunostained for the low-affinity nerve growth factor receptor (p75-NGFR) as an index of pulpal ageing; and an extensive decrease was found in the old adult as compared to young adult rats. These results indicate that old rats maintain the capacity for nerve sprouting despite the decreases in p75-NGFR labelling of pulp cells, pulp volume and nerve fibre numbers that occur as part of dental ageing.
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PMID:Effect of ageing on responses of nerve fibres to pulpal inflammation in rat molars analysed by quantitative immunocytochemistry. 128 28

We have generated mice carrying a mutation of the gene encoding the low affinity NGF receptor p75NGFR by targeted mutation in embryonic stem cells. Mice homozygous for the mutation were viable and fertile. Immunohistochemical analyses of the footpad skin of mutant mice revealed markedly decreased sensory innervation by calcitonin gene-related peptide- and substance P-immunoreactive fibers. The defective innervation was correlated with loss of heat sensitivity and associated with the development of ulcers in the distal extremities. Complicated by secondary bacterial infection, the ulcers progressed to toenail and hair loss. Crossing a human transgene encoding p75NGFR into the mutant animals rescued the absent heat sensitivity and the occurrence of skin ulcers and increased the density of neuropeptide-immunoreactive sensory innervation of footpad skin. The mutation in the gene encoding p75NGFR did not decrease the size of sympathetic ganglia or the density of sympathetic innervation of the iris or salivary gland. Our results suggest that p75NGFR has an important role in the development and function of sensory neurons.
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PMID:Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. 131 67

Immunocytochemical expression of the low-affinity nerve growth factor receptor was studied in human fetal and adult tissues using the monoclonal antibody ME20.4. In dorsal root ganglia, a few immunoreactive neurons were first detected in nine-week-old fetuses and many more were found in the following weeks of gestation. However, none was present in adult ganglia. The ME20.4-positive cells were larger than neurons immunostained by substance P, calcitonin gene-related peptide or galanin antibodies. In the spinal cord, fibres immunostained by ME20.4 appeared in a characteristic pattern that differed from the spatial and temporal distributions of synaptophysin- and neurofilament-immunoreactive fibres. Those expressing the low-affinity nerve growth factor receptor were only detected in regions containing collaterals of primary sensory axons: (i) in the dorsal funiculus between seven and 18 weeks of gestation; (ii) in a ventrodorsal bundle reaching the ventral horn from weeks 12-14; (iii) in the medial region of the dorsal horn between weeks 12 and 20; (iv) in the superficial layers and lateral portion of the dorsal horn after the 14th week of gestation and also in adult spinal cord. During the fetal period, ME20.4 immunoreactivity was also found in motoneurons and peripheral nerve fibres in the skin, myotomes and gut. Sheaths of peripheral nerves and the adventitia of blood vessels were stained both in fetal and adult tissues. Thus, the low-affinity nerve growth factor receptor is: (i) strongly expressed in the developing human nervous system; (ii) transiently associated with a subset of large primary sensory neurons and with motoneurons; (iii) transiently and sequentially expressed by various groups of sensory afferents to the spinal cord; (iv) permanently expressed by fibres in the superficial layers of the dorsal horn, Clarke's column, nerve sheaths and the adventitia of blood vessels.
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PMID:Developmental pattern and distribution of nerve growth factor low-affinity receptor immunoreactivity in human spinal cord and dorsal root ganglia: comparison with synaptophysin, neurofilament and neuropeptide immunoreactivities. 143 99

The distribution of nerve growth factor receptor (NGF receptor)-like immunoreactivity in pulps of developing primary and mature permanent cat canine teeth was examined, by use of a monoclonal antibody against NGF receptor detected by fluorescence immunohistochemistry and pre-embedding immunocytochemical light- and electron microscopy. Both primary and permanent pulps contained a vast number of NGF receptor-like immunoreactive nerves. Immunolabelling appeared to be localized both to axons and Schwann cells. In addition, many blood vessel walls in immature primary tooth pulps showed NGF receptor-like immunoreactivity, in contrast to permanent pulps where blood vessels rarely were NGF receptor-immunoreactive. Double-labelling immunofluorescence experiments revealed that in the permanent pulp a majority of the NGF receptor-positive nerves also showed calcitonin gene-related peptide (CGRP)-like immunoreactivity, and many showed substance P-like immunoreactivity. However, nerve fibers with neuropeptide Y-like immunoreactivity lacked NGF receptor-like immunoreactivity. In developing primary tooth pulps fewer NGF receptor-positive nerves were CGRP-like immunoreactive or substance P-like immunoreactive, as compared to the permanent pulp. Neuropeptide Y-like immunoreactive nerve fibers were not detected in the primary tooth pulp. The results suggest a role for nerve growth factor in both developing and mature sensory nerves of the tooth pulp.
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PMID:Nerve growth factor receptor-like immunoreactivity in primary and permanent canine tooth pulps of the cat. 165 63

The chapter reviews some of recent evidence which suggests that one neurotrophin, nerve growth factor (NGF), is a peripherally produced mediator of some persistent pain states, notably those associated with inflammation. The evidence for this proposal is as follows. 1. The endogenous production of NGF regulates the sensitivity of nociceptive systems. Behavioural and electrophysiological studies have shown that sequestration of constitutively produced NGF leads to decrease nociceptor sensitivity. 2. In a wide variety of experimental inflammatory conditions NGF levels are rapidly increased in the inflamed tissue. 3. The high-affinity NGF receptor, trkA, is selectively expressed by nociceptive sensory neurons particularly those containing sensory neuropeptides such as substance P and CGRP. 4. The systematic or local application of exogenous NGF produces a rapid and prolonged behavioural hyperalgesia in both animals and humans. Exogenous NGF has also been found to activate and sensitize fine calibre sensory neurons. 5. In a number of animal models, much of the hyperalgesia associated with experimental inflammation is blocked by pharmacological "antagonism' of NGF. The mechanisms by which NGF up-regulation in inflamed tissues might lead to sensory abnormalities is also discussed. In particular, evidence is reviewed which suggests that increased NGF levels leads to both peripheral sensitization of nociceptors and central sensitization of dorsal horn neurons responding to noxious stimuli.
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PMID:NGF as a mediator of inflammatory pain. 873 Jul 82

Spontaneous cellular reorganisation at the lesion site has been investigated following massive spinal cord compression injury in adult rats. By 2 days post operation (p.o.), haemorrhagic necrosis, widespread axonal degeneration, and infiltration by polymorphnuclear granulocytes and OX42-positive macrophages were observed in the lesion site. By 7 days p.o., low affinity nerve growth factor receptor-positive Schwann cells, from activated spinal roots, were identified as they migrated far into the lesion. Between 7 and 14 days p.o., the overlapping processes of Schwann cells within the macrophage-filled lesion formed a glial framework which was associated with extensive longitudinally orientated ingrowth by many neurofilament-positive axons. Relatively few of these axons were calcitonin gene-related peptide (CGRP)-, substance P (SP)-, or serotonin (5HT)-positive; however, many were glycinergic or gamma aminobutyric acid (GABA)ergic. At 21 and 28 days p.o. (the longest survival times studied), a reduced but still substantial amount of orientated Schwann cells and axons could be detected at distances of up to 5 mm within the lesion. Glial fibrillary acidic protein (GFAP) immunoreactivity demonstrated the slow formation of astrocytic scarring which only became apparent at the lesion interface between 21 and 28 days p.o. The current data suggest the possibility of developing future therapeutic strategies designed to maintain or even enhance these spontaneous and orientated regenerative events.
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PMID:Spontaneous longitudinally orientated axonal regeneration is associated with the Schwann cell framework within the lesion site following spinal cord compression injury of the rat. 967 Sep 92

Estrogen status has profound effects on cutaneous sensitivity in adult female rats. The presence of alpha-estrogen receptor mRNA and protein in NGF-dependent, adult female rat dorsal root ganglion (DRG) neurons raises the possibility that estrogen modulates cutaneous sensation by acting directly on primary afferent neurons, perhaps by altering their sensitivity to NGF. The present study examined the effect of long-term (90 days) daily injections of an estrogen preparation, Premarin (Wyeth-Ayerst, Radnor, PA), to ovariectomized adult rats on lumbar DRG high-affinity NGF receptor, trkA, mRNA levels, and on beta-preprotachykinin (beta-PPT) mRNA levels, which have been shown to be regulated by NGF. Two doses were used in the experiments, the higher dose being 10 times that of the lower dose. Such injections had an effect opposite that reported for short-term, acute estrogen treatment on DRG trkA mRNA levels. The current data show that long-term daily estrogen treatment decreases trkA mRNA levels by 36%. After 90 days of estrogen treatment, no dose effect was evident. Moreover, as would be expected if beta-PPT gene expression is regulated by NGF through the trkA receptor, long-term estrogen treatment decreased DRG neuronal beta-PPT mRNA levels by about 30%. As with trkA, there was no dose effect evident after 90 days of estrogen treatment. These data suggest the possibility that estrogen modulates DRG neuropeptide gene expression and, perhaps, cutaneous sensitivity by regulating NGF receptor gene expression.
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PMID:Long-term estrogen replacement coordinately decreases trkA and beta-PPT mRNA levels in dorsal root ganglion neurons. 1007 1

Effects of delivery of nerve growth factor, from a catheterized osmotic mini-pump to the proximal stump of a transected sciatic nerve, were compared with the effects of normal saline. A pilot measured retrograde axonal transport of nerve growth factor to determine a pump concentration which raised axonal transport ipsilaterally, but not contralaterally. The effects of this delivery over 12 days were then determined on expression of growth-associated protein-43, trkA, p75NTR and preprotachykinin A ipsilateral and contralateral to the pump in dorsal root ganglia at L4 and L5 (pooled). Ganglionic expression was measured both as messenger RNA and protein. Axotomy (saline pumps) increased growth-associated protein-43 messenger RNA (318 +/- 14%: all changes are percent of contralateral, non-axotomized ganglia with saline pumps) and immunoreactivity (431 +/- 43%). The increase was significantly less (P < 0.001) ipsilateral to nerve growth factor pumps (191 +/- 45%). Axotomy reduced expression of p75NTR (messenger RNA: 52 +/- 17%, P < 0.01; immunoreactivity: 74 +/- 3%, P < 0.05). These decreases were converted to increases by nerve growth factor delivery (respectively 143 +/- 40% and 281 +/- 67%; both P < 0.01). With trkA, axotomy decreased the expression of the messenger RNA (68 +/- 40%, P < 0.01) and of the primary translation product--110,000 mol. wt protein (55 +/- 12%, P < 0.01)--but not the fully glycosylated trkA protein (mol. wt 145,000). Nerve growth factor delivery did not affect trkA expression. Axotomy reduced messenger RNA for the substance P precursor, preprotachykinin A, to 42 +/- 17% (P < 0.01) and this reduction was prevented by nerve growth factor treatment. We suggest that the primary effect of nerve growth factor on axotomized C-fibres is not to promote regeneration, although that may be its secondary effect via an action on Schwann cells. It is possible that reduced neuronal sensitivity to nerve growth factor during regeneration is advantageous in suppressing nociception.
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PMID:Focally administered nerve growth factor suppresses molecular regenerative responses of axotomized peripheral afferents in rats. 1033 76

Repetitive noxious stimulation leads to permanent adaptive changes of central pathways involved in the genesis and integration of nociception. Several classes of neurotrophic factors that affect brain plasticity are also involved in the regulation of sensory functions in adulthood. To investigate a putative role of nerve growth factor (NGF) in central plasticity linked to chronic pain, modifications in immunoreactivity (IR) for the high-affinity NGF receptor, TrkA, were studied at spinal levels in a rat model of inflammatory chronic pain, adjuvant-induced arthritis (AIA). We report a specific increase in the number of TrkA-IR profiles in laminae V-VI at lumbar levels L3 and L4 in arthritic rats. Tract tracing using FluoroGold injections in the ventrobasal complex of the thalamus and in the brainstem showed that these increased TrkA-IR profiles are spinoreticular neurons. Dual labeling with calcitonin gene-related peptide or substance P showed that TrkA-IR neurons were mainly located in projection fields of small- to medium-sized primary afferent fibers, which convey nociceptive inputs. These results suggest that TrkA-containing neurons of the spinal dorsal horn participate in the first central relay of transmission of nociceptive information to supraspinal centers. Enhanced numbers of TrkA-IR neurons during AIA strongly support the hypothesis of a participation of NGF in adaptive mechanisms of central nociceptive pathways observed in chronic pain states.
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PMID:Chronic pain is associated with increased TrkA immunoreactivity in spinoreticular neurons. 1037 57

Women have a higher incidence of inflammatory disorders than men and also appear to perceive painful stimuli differently. It has been suggested that neuroinflammation plays a role in painful bladder disorders of uncertain etiology, such as interstitial cystitis. Nerve growth factor (NGF) is a neurotrophin produced in peripheral tissues that can also mediate pain and inflammation. We found that treatment of mice with the estrogen antagonist ICI 182,780 had no effect on bladder NGF content but decreased bladder NGF messenger RNA. Using immunohistochemistry, we demonstrated that the mucosa is the primary source of NGF in the mouse bladder, and the bladder mucosa also expresses estrogen receptor (ER)-alpha, ER-beta, and the high-affinity NGF receptor tyrosine kinase A. Estrogen may also modulate neurogenic inflammation by interaction with other substances and cells that participate in the pathogenesis of neurogenic inflammation, including substance P, bradykinin, and mast cells. Collectively, these observations indicate that estrogen has the capacity to influence the onset and course of neurogenic inflammation of the bladder.
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PMID:Estrogen and neuroinflammation. 1137 49


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