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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spinal pia mater receives a rich innervation of small sensory axons via the ventral roots. Other sensory axons enter the ventral roots but end blindly or turn abruptly in hairpin loop-like formations and continue in a distal direction. In the present study, the content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, growth-associated protein (GAP-43)-, and low-affinity neurotrophin receptor protein (p75NGFr)-like immunoreactivity (-LI) associated with these different types of sensory axons was assessed with light and electron microscopic immunohistochemical techniques. In addition, the binding of antibodies against synthetic peptides representing unique sequences of residues in the products of the trk and trkB protooncogenes was analyzed. These genes encode membrane spanning proteins, which have been shown to constitute specific high affinity binding sites for several members of the nerve growth factor family of neurotrophic factors. The results of the present study imply that the ventral root afferents comprise several different types of sensory axons, which all contain SP-, CGRP-, GAP-43-, and p75NGFr-like immunoreactivities. In addition, at least some of the presumed sensory fiber bundles in ventral roots and the pia mater were immunoreactive for the trkB gene product. Moreover, leptomeningeal cells and nonneuronal cells of the ventral roots were shown to bind antibodies to both the trk and trkB gene products. The ventral root afferents seem to share their immunohistochemical pattern with pain-transducing axons at some other locations, such as the tooth pulp. The contents of SP- and CGRP-LI in sensory axons that reach the central nervous system (CNS) through the ventral root indicate that ventral root afferents may be involved in sensory mechanisms, such as the ventral root pain reaction, as well as in the control of the pial blood vessels. The demonstration of GAP-43 and neurotrophin receptor-immunoreactivities associated with unmyelinated fibers in ventral roots and the pia mater is discussed in relation to previous reports on postnatal plasticity in these axonal populations.
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PMID:Substance P-, calcitonin gene-related peptide, growth-associated protein-43, and neurotrophin receptor-like immunoreactivity associated with unmyelinated axons in feline ventral roots and pia mater. 751 Jul 31

Experimental inflammation produced by an intraplantar injection of complete Freund's adjuvant results in local sensory hypersensitivity and up-regulates the neuropeptides substance P and calcitonin gene related peptide in the primary sensory neurons innervating the inflamed tissue. The inflammation also elevates nerve growth factor levels in the skin. Systemic administration of anti-NGF neutralizing antibodies prevent the behavioral sensitivity, the up-regulation of neuropeptides and the inflammation-induced expression of the immediate early gene c-fos in dorsal horn neurons, without modifying swelling and erythema. Elevation of the neurotrophin NGF in the periphery is a major contributor, therefore, of inflammatory pain.
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PMID:Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. 753 Mar 42

Distinct classes of primary sensory neurons in dorsal root ganglia subserve different sensory modalities, terminate in different dorsoventral locations in the spinal cord, and display different neurotrophin response profiles. Large diameter muscle afferents that terminate in the ventral spinal cord are NT-3 responsive, whereas small diameter afferents subserving pain and temperature are NGF responsive and terminate in the dorsal spinal cord. Previous in vitro studies showed that the developing ventral spinal cord secretes a diffusible factor that inhibits the growth of sensory axons. Here we show that this factor repels NGF-responsive axons but has little effect on NT-3-responsive axons. We also provide evidence implicating semaphorin III/collapsin, a diffusible guidance molecule expressed by ventral spinal cord cells, in mediating this effect. These results suggest that semaphorin III functions to pattern sensory projections by selectively repelling axons that normally terminate dorsally.
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PMID:Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord. 774 62

During vertebrate development, naturally occurring neuronal cell death is regulated by target-derived peptide factors, called neurotrophins. A recent series of papers describe the phenotypes of germline-targeted mutant mice deficient in neurotrophins and their receptors. Histological analysis of these mice for the first time has provided knowledge about the specific neuron populations that are dependent on neurotrophin action for development. Mice deficient for nerve growth factor (NGF) and its high-affinity receptor, encoded by the trkA proto-oncogene, suffer from complete loss of sympathetic neurons and sensory neurons responsive to temperature and pain. Mice deficient for brain-derived neurotrophic factor (BDNF) and its receptor, encoded by the trkB gene, display loss of sensory neurons responsive to tactile stimuli. In addition, trkB mutant mice experience loss of motor neurons indicating a possible specific function of the second TrkB ligand, neurotrophin-4 (NT-4), in motor neuron development. Mice deficient for neurotrophin-3 (NT-3) and its receptor, encoded by the trkC gene, show abnormal movements caused by the loss of sensory proprioceptive neurons.
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PMID:Role of neurotrophins in mouse neuronal development. 805 Jun 73

Congenital insensitivity to pain with anhidrosis (CIPA; MIM 256800) is an autosomal-recessive disorder characterized by recurrent episodes of unexplained fever, anhidrosis (absence of sweating) and absence of reaction to noxious stimuli, self-mutilating behaviour and mental retardation. The genetic basis for CIPA is unknown. Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. Mice lacking the gene for TrkA, a receptor tyrosine kinase for NGF, share dramatic phenotypic features of CIPA, including loss of responses to painful stimuli, although anhidrosis is not apparent in these animals. We therefore considered the human TRKA homologue as a candidate for the CIPA gene. The mRNA and genomic DNA encoding TRKA were analysed in three unrelated CIPA patients who had consanguineous parents. We detected a deletion-, splice- and missense-mutation in the tyrosine kinase domain in these three patients. Our findings strongly suggest that defects in TRKA cause CIPA and that the NGF-TRKA system has a crucial role in the development and function of the nociceptive reception as well as establishment of thermoregulation via sweating in humans. These results also implicate genes encoding other TRK and neurotrophin family members as candidates for developmental defect(s) of the nervous system.
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PMID:Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. 869 25

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

Inflammation results in an early and maintained elevation in nerve growth factor (NGF) levels in inflamed tissues. Neutralizing the action of the increased NGF with specific anti-NGF antibodies substantially diminishes inflammatory hypersensitivity, indicating that this neurotrophin is a key mediator in the production of inflammatory pain. The hyperalgesic actions of NGF may in part be the consequence of an increase in sensitivity of the peripheral terminals of high threshold nociceptors either as a result of a direct action of NGF on trkA expressing sensory fibres or indirectly via the release of sensitizing mediators from trkA expressing inflammatory cells and postganglionic sympathetic neurons. NGF is also, however, retrogradely transported in sensory neurons to the dorsal root ganglion where it alters transcription of a number of proteins and peptides. This chapter reviews evidence suggesting that an NGF-mediated modification of gene expression in the dorsal root ganglion during inflammation is central to the pathophysiology of persistent pain. The phenotype changes produced by NGF during inflammation include elevation of neuropeptides which may amplify sensory input signals in the spinal cord and augment neurogenic inflammation in the periphery and the upregulation of growth related molecules which may lead to a hyperinnervation of injured tissue by promoting terminal sprouting.
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PMID:Phenotypic modification of primary sensory neurons: the role of nerve growth factor in the production of persistent pain. 873 Jul 83

Immunotoxins have been used to study the targeting of biologically active substances at neurons in vivo and to make experimental neural lesions. OX7-saporin, directed against Thy 1, destroys any neuron. 192 IgG-saporin, directed against the 'low affinity' neurotrophin receptor (p 75NTR), selectively destroys neurons expressing this receptor (sympathetic, sensory, cholinergic basal forebrain, cerebellar Purkinje). Anti-D beta H-saporin, directed against dopamine beta-hydroxylase, the enzyme that converts dopamine to norepinephrine, selectively destroys noradrenergic neurons (sympathetic, CNS). These agents show that several types of neural antigens may prove useful in treating pain, and anti-D beta H-saporin may be active against pheochromocytoma or neuroblastoma.
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PMID:Targeting toxins to neural antigens and receptors. 874 May 62

Previous studies suggest that NGF may function as a mediator of inflammatory pain. Here, we examined the effect of inflammation on expression of the low affinity neurotrophin receptor p75, using the model of cyclophosphamide-induced cystitis in rats. In control rats, p75-positive thick fibre bundles were scattered in the muscle layer. At 2 and 3 days after injection of cyclophosphamide, numbers of p75-positive fine fibres in the muscle layer were dramatically increased. Electron microscopy revealed that p75 immunoreactivity was localized on the surface of Schwann cells and at the sites where they were apposed to axons. Results show that p75 is up-regulated in inflamed tissues, suggesting that p75 may bind to and take up nerve growth factor (NGF), thus participating in NGF-induced hyperalgesia.
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PMID:Increase of p75 immunoreactivity in rat urinary bladder following inflammation. 881 19

The NTRK1 gene encodes one of the receptors for the Nerve Growth Factors and it is located at 1q21-22. Rearrangements of NTRK1 are frequently detected in human papillary thyroid carcinoma and lead to the formation of chimeric oncogenes, similarly to what observed for the other neurotrophin receptor RET. In addition, the two receptor genes are target of point mutations associated with different human diseases. RET is affected by germ line and somatic mutations in MEN2A, MEN2B tumor syndromes and in the abnormal developmental Hirschsprung disease, whereas mutations of NTRK1 have been reported very recently in patients with congenital insensitivity to pain with anidrosis (CIPA). With the aim to provide a tool for searching mutations along the whole NTRK1 gene, we have determined its genomic organization. Our results demonstrated that NTRK1 is contained within 25 Kb of DNA and is organized in 17 exons, one of which is alternatively spliced. The sequence of the 5' flanking region indicates a high content in C/G, the absence of TATA box, the presence of several putative binding sites for Sp1, AP1, AP2, AP3, ATF and GCF transcription factors.
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PMID:Genomic organization of the human NTRK1 gene. 895 89


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