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)

Peripheral nerve lesions cause retrograde changes in the spinal cord, involving initially the descending serotoninergic pathways and later the substance P sensory input and methionine-enkephalin interneurons. Within 48 h after sciatic nerve resection there is a significant increase of 5-hydroxyindoleacetic acid in the lumbar spinal cord with no changes of serotonin metabolism in the cell body areas. The immunocytochemical analysis of the spinal cord shows that 20 days after nerve lesion there is a loss of substance P-positive boutons in the laminae I and II of the dorsal horn in the lumbar segment. Such a morphological change is correlated by radioimmunoassay for substance P and methionine-enkephalin, that reveals a significant loss of both peptides. Treatment with acetyl-L-carnitine prevents the early 5-hydroxyindoleacetic acid increase and the reduction of peptide content observed 20 days after lesioning the sciatic nerve. These data suggest that treatment with acetyl-L-carnitine exerts a neuroprotective activity preventing the retrograde changes triggered by peripheral nerve lesions.
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PMID:Intraspinal degenerative atrophy caused by sciatic nerve lesions prevented by acetyl-L-carnitine. 128

Immunohistochemistry has been used to study, the capacity of different types of sensory axons in the saphenous nerve to extend into denervated glabrous skin territory after a chronic sciatic nerve lesion. In this study, the extension of the intact or regenerating thin peptidergic and coarse saphenous nerve fibres in adult and neonatal rats was determined. Substance P (SP) and calcitonin gene-related peptide (CGRP) antibodies were used as markers for thin axons and neurofilament (NF) antibodies for coarse axons. In addition, S-100 protein (S-100) antibodies, which primarily stain Schwann cells associated with myelinated axons, as well as innervated lamellated cells of Meissner corpuscles, were used. After a chronic sciatic nerve lesion in adult rats, thin dermal and epidermal SP-immunoreactive (IR) and CGRP-IR saphenous nerve fibres were present in an area lateral to that normally innervated by the saphenous nerve in the foot sole. In neonatally lesioned animals, thin dermal and epidermal SP-IR and CGRP-IR, as well as coarse dermal NF-IR fibres and S-100-IR cells, all of which derived from the saphenous nerve, were found in the sciatic nerve territory. In addition, some dermal SP-IR and CGRP-IR fibres were transiently present in the lateral part of the foot sole. After chronic sciatic nerve lesion and a concomitant crush injury of the saphenous nerve in adults or neonatals, thin dermal and epidermal SP-IR and CGRP-IR fibres, as well as coarse dermal NF-IR fibres and S-100-IR cells, were found in the innervation area normally occupied by the sciatic nerve. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in adult rats, the SP-IR and CGRP-IR fibres, as well as the NF-IR fibres and S-100-IR cells were restricted to the medial part of this area. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in neonatal rats, a few thin dermal SP-IR and CGRP-IR fibres were found in the lateral part of the foot sole as well. The findings of the present study together with those of previous morphological studies indicate that intact thin axons from the saphenous nerve, including those exhibiting peptide immunoreactivity, but not coarse saphenous axons, are capable of extending into "foreign" denervated glabrous skin after chronic sciatic nerve injuries. In neonatally sciatic-nerve-injured animals, both groups of axons spread from the intact saphenous nerve into the sciatic nerve territory.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Collateral reinnervation and expansive regenerative reinnervation by sensory axons into "foreign" denervated skin: an immunohistochemical study in the rat. 130 74

Cryotherapy has been clinically applied to relieve pain by blocking peripheral nerve function. Clinically, analgesia has been successfully achieved but there is suggestion that permanent pain relief may be accompanied by extended motor and sensory deficits. This study was undertaken to determine the effect of a peripheral cryogenic nerve lesion, i.e., of the sciatic nerve, on behavioral effects and substance P content in the dorsal horn of the spinal cord. In rats, the right sciatic nerve was exposed and cryolesioned using one freeze-thaw-refreeze cycle. In an alternate group, the right sciatic nerve was cut and a 3-mm region was excised. Animals were allowed to recover 7 or 21 days during which their behavior was assessed. Autotomy, an animal's tendency to attack the nerve-injured affected limb, occurred in both the cryolesioned and sectioned groups. They were killed by transcardiac perfusion of fixative and segments L4-S1 were processed for immunocytochemistry. The SP-like immunoreactivity (SPLI) in the right and left dorsal horns was compared and quantitated using a microcomputer imaging device. We utilized a fully automated program to digitize and quantitate the staining of the substantia gelatinosa. There was no significant difference in SPLI in the dorsal horns of the sham-operated controls at either time period. At 7 days the sectioned group demonstrated a 40% decrease in SPLI and 76% decrease at 21 days. In the cryolesioned group, there was a 34% decrease at 7 days and by 21 days there was a 68% decrease in immunoreactivity on the operated side.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autotomy and decreased spinal substance P following peripheral cryogenic nerve lesion. 172 66

The changes in gene expression and protein synthesis induced in neurons by axotomy usually lead to increased production of axon constituents and decreased production of molecules related to neurotransmission. Exceptions to this generalization occur, however, and it is unclear whether the injury itself changes the pattern of synthesis or whether individual mechanisms regulate the synthesis of the various axonal components. We used in situ hybridization histochemistry and immunocytochemistry to compare the changes in L4 and L5 rat dorsal root ganglion neuron levels of preprotachykinin mRNA and tachykinin peptides caused by sciatic nerve injury with those caused by dorsal root injury. Both lesions elicit regeneration, although only the axotomized peripheral processes re-establish functional contact with their targets. In the contralateral, intact dorsal root ganglia approximately 17% of neurons contained detectable levels of both mRNAs and peptides. Sciatic nerve section decreased by 70% the number of neurons labeled for preprotachykinin mRNA at three days post-operatively. Not all cells in the ganglion are axotomized by the sciatic nerve lesion; grain counts over the cells spared by the lesion showed an increased level of labeling, possibly a result of collateral sprouting by these spared cells. By two weeks, the number of cells labeled for preprotachykinin mRNA had decreased to 80% of control levels. The numbers of neurons labeled for tachykinin peptides decreased more slowly and reached approximately 50% of control numbers at two weeks. By six months post-operatively, when regeneration is largely complete, the number of neurons containing both mRNAs and peptides returned to normal. In contrast, dorsal root section did not elicit a decrease in the number of neurons labeled either for the mRNAs or the peptides at any of the post-operative intervals examined. These results indicate that axotomy is not the stimulus that elicits changes in the expression of genes coding for tachykinins. Evidence is considered indicating that interruption of the supply of peripherally derived nerve growth factor may be responsible for the changes in gene expression for tachykinins after axotomy.
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PMID:Expression of beta-preprotachykinin mRNA and tachykinins in rat dorsal root ganglion cells following peripheral or central axotomy. 209 25

The multiple and diverse roles played by neuropeptide Y, vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide and other biologically active peptides in the cardiovascular system are considered. A model of the vascular neuroeffector junction is described, which illustrates the interactions of peptidergic and nonpeptidergic transmitters that are possible at pre- and postjunctional sites. The effects of peptides on specific endothelial receptors are also described, which highlights the ability of these agents to act as dual regulators of vascular tone at both adventitial and intimal surfaces, following local release from nerves, or from endothelial cells themselves. Changes in expression of vascular neuropeptides that occur during development and aging in some disease situations and following nerve lesion are discussed.
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PMID:Peptides and vasomotor mechanisms. 218 71

The substance P and Met-enkephalin content were measured in the rat lumbar spinal cord after monolateral section of the sciatic nerve. The proximal stump of the lesioned nerve was either ligated, limiting the formation of neuroma, or sutured intraperitoneally, allowing the formation of a very large neuroma. Both types of lesion caused a similar peptide loss. Substance P and Met-enkephalin decreased by about 50% 10 days following the lesion. Such a loss was maintained even 30 days postoperatively and was not affected by the neuroma size. Immunohistochemical stainings showed that the loss of both peptides occurred in laminae I and II of the dorsal horn. It is suggested that pain sensation developing after peripheral nerve lesion may be due to the intraspinal loss of enkephalin rather than to the neuroma formation.
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PMID:Peripheral nerve lesions cause simultaneous alterations of substance P and enkephalin levels in the spinal cord. 241 40

We have investigated the reversibility and prevention of peptidergic losses in the lumbar spinal cord caused by permanent resection of sciatic nerve. The lesion triggers a series of degenerative events involving the substance P sensory imput as well as met-enkephalin interneurons of the substantia gelatinosa. The degenerative processes are evident 10 days after sciatic nerve lesion and are gradually reversible as shown by radioimmunoassay and quantitative immunocytochemistry. Recovery begins 30 days postlesioning and full restoration is observed at 90 days. Serotonin (5-HT) turnover is markedly affected by sciatic nerve lesion as soon as 24 hr postlesioning, when 5-HT metabolism is enhanced, returning to control levels just preceding the peptide alterations; 5-HT metabolism then undergoes a transient period of hypoactivity which correlates with the beginning of the peptidergic restorative processes. Altogether these results, with previous observations showing that 5-HT depletion prevents metenkephalin interneurons degeneration triggered by the lesion (Di Giulio et al.: J Neurosci Res 18:443-448, 1987), suggest a role for 5-HT in the synaptic plasticity of the substantia gelatinosa of the spinal cord. The administration of gangliosides (10 or 50 mg/kg) to sciatic-nerve-lesioned animals fully prevented the metenkephalinergic degeneration without affecting the degenerative atrophy of the lesioned substance P sensory imput.
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PMID:Reversibility and prevention of intraspinal peptidergic loss caused by sciatic nerve lesions. 246 8

The sciatic nerve was sectioned unilaterally in rats and nerve growth factor (NGF) applied locally to the nerve stump for the following 10-14 days using an indwelling osmotic pump. The aim of the experiment was to test whether NGF had any effect on the previously reported neurophysiological and neurochemical events that occur central to a peripheral nerve lesion. The method of application allowed the sciatic nerve on the other side to be used as a control. Primary afferent depolarization fell, as expected, to 13% of its control value after chronic nerve section but if NGF was administered it fell to only 43.5% of control. Chronic nerve section is also known to result in expansion of the receptive fields of deafferented dorsal horn cells. NGF treatment reduced the number of such large receptive fields by 50%. The normal depletion of fluoride resistant acid phosphatase from the cut nerve terminals in the dorsal horn did not occur following NGF treatment. Radioimmunoassay of substance P revealed that the 30% reduction in dorsal horn levels that follows chronic sciatic nerve section did not occur when NGF was applied and that the accompanying 60% decrease in dorsal root ganglion levels was changed to a 64% increase by NGF. The results show that chronic NGF treatment of a cut sciatic nerve does partially reverse the central changes that normally follow deafferentation.
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PMID:Nerve growth factor counteracts the neurophysiological and neurochemical effects of chronic sciatic nerve section. 258 48

The presence of substance P-immunoreactive (SPI) varicose nerve networks and nerve fiber bundles in guinea pig prevertebral sympathetic ganglia has been confirmed by fluorescence immunohistochemistry. No SPI neurons have been found in sympathetic ganglia, including lumbar paravertebral ganglia. Peroxidase-antiperoxidase immunocytochemical methods have shown that SPI nerve terminal varicosities in the inferior mesenteric ganglion (IMG) form morphologically identifiable synapses on dendritic shafts. Cutting the intermesenteric nerve produces no obvious change in SP immunoreactivity in the IMG; cutting the lumbar splanchnic nerves produces nearly total depletion which becomes virtually complete if the two lesions are combined; SP immunoreactivity accumulates in the central ends of the lumbar splanchnic nerves and in the cranial end of the intermesenteric nerve. Cutting hypogastric nerves or colonic branches of the IMG leads to accumulation of SP immunoreactivity in their ganglionic stumps and to build-up (colonic nerve lesion) rather than depletion of SP immunoreactivity in the IMG. Capsaicin treatment leads to total loss of SP immunoreactivity from the prevertebral ganglia and dorsal root ganglia, severe depletion in laminae I and II and dorsolateral fasciculus of the spinal cord, and total loss from perivascular and paravascular networks of the ileum and mesentery, with sparing of the SP immunoreactivity of the enteric nerve plexuses. Capsaicin is thought to deplete sensory neurons selectively. Removal of the spinal cord below T7 without damage to the dorsal root ganglia leaves the intraganglionic SPI nerve networks and bundles intact. We conclude that these are derived from peripheral processes of sensory neurons and we propose that the SPI synapses in the IMG arise from collateral branches of these sensory peripheral processes. This implies a novel role for these processes, in forming intraganglionically in the prevertebral ganglia synapses which may take part in the reflex control of the viscera, independently of the central nervous system.
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PMID:Substance P-immunoreactive peripheral branches of sensory neurons innervate guinea pig sympathetic neurons. 617 70

The nature of the association of substance P (SP) with taste buds in the rat tongue was investigated by immunohistochemical and radioimmunoassay techniques. Both the circumvallate and fungiform papillae were found to receive a rich innervation by substance P-containing fibres. Although these fibres were closely associated with the taste buds in these structures, they assumed a perigemmal rather than an intragemmal location. Bilateral lesions of the glossopharyngeal nerve resulted in the depletion of taste buds from the vallate papilla and a large reduction in substance P immunoreactive fibres in this area. Lesions of the chorda tympani, which led to the degeneration of taste buds in fungiform papillae, had no effect on the immunohistochemical appearance of substance P in these papilla or on the substance P levels in the anterior part of the tongue. Lesions of the mandibular division of the trigeminal nerve or neonatal capsaicin treatment had no effect on the structural integrity of taste buds in fungiform papillae but led to the depletion of substance P-immunoreactive fibres from these papillae. Both of these procedures caused a 71% reduction in the substance P content of the anterior tongue, ipsilaterally after the nerve lesion and bilaterally after capsaicin treatment. The results are discussed in relation to the possible functional role of substance P-containing fibres within nerves supplying taste structures of the tongue.
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PMID:The nature of the substance P-containing nerve fibres in taste papillae of the rat tongue. 618 43


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