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 most common form of peripheral neuropathy is that associated with diabetes mellitus. In rodent models of diabetes there are expression deficits in nerve growth factor (NGF) and in its high-affinity receptor, trkA, leading to decreased retrograde axonal transport of NGF and decreased support of NGF-dependent sensory neurons, with reduced expression of their neuropeptides, substance P and calcitonin gene-related peptide (CGRP). Treatment of diabetic rats with intensive insulin normalized these deficits and treatment with exogenous NGF caused dose-related increases, giving levels of NGF and neuropeptides which were greater than those of controls. Neurotrophin-3 (NT-3) mRNA was also deficient in leg muscle from diabetic rats and administration of recombinant NT-3 to diabetic rats increased the conduction velocity of sensory nerves without affecting motor conduction velocity. These findings implicate deficient neurotrophic support in diabetic neuropathy and suggest that its correction should be a paramount therapeutic target.
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PMID:Neurotrophins and peripheral neuropathy. 873 Jul 85

This study monitored the extranuclear endogenous mono ADP-ribosylation of proteins. At least 10 proteins were ADP-ribosylated in a crude extract from control superior cervical ganglia, and 7 were labeled in control dorsal root ganglia; whereas in the diabetic rat the extent of labeling was reduced. These data suggest that proteins of peripheral ganglia are excessively ADP-ribosylated in vivo. Treatment of diabetic animals with silybin, a flavonoid with ADP-ribosyltransferase inhibitory activity, did not affect hyperglycemia, but prevented the alterations in the extent of mono-ADP-ribosylation of proteins. This effect was associated with the prevention of substance P-like immunoreactivity loss in the sciatic nerve. In the membrane fraction of sciatic nerve Schwann cells, at least 9 proteins were ADP-ribosylated, in diabetic rats the extent of labeling was increased. A comparable increase involving the same proteins was triggered by chronic nerve injury and by corticosteroid treatment. Silybin treatment of diabetic rats prevented such an increase. We propose that the inhibition of excessive protein mono-ADP-ribosylation by silybin prevented the onset of diabetic neuropathy, while the silybin effect on mono-ADP-ribosylation of Schwann cells is likely indirect and secondary to the improvement of diabetic axonopathy.
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PMID:Alterations of protein mono-ADP-ribosylation and diabetic neuropathy: a novel pharmacological approach. 888 32

We examined and compared a mechanosensitive human sural neuroma and a contralateral sural nerve collected simultaneously from a patient involved in a diabetic neuropathy research protocol. Using indirect immunofluorescence staining. we identified a striking difference in the content within axons of two neuropeptides, substance P (SP) and calcitonin, gene-related peptide (CGRP), between the contralateral nerve and the neuroma. Unlike the contralateral nerve, where immunofluorescence was sparse, a significant number of disorganized axon profiles that stained brightly positive for CGRP or SP were identified in the neuroma. In contrast, staining for tyrosine hydroxylase, a label of sympathetic axons, was largely absent except around one large arteriole. The neuroma specimen also contained large numbers of serotonin-containing mast cells, only noted occasionally in the contralateral nerve. The peptide staining and mast cell accumulation in the human neuroma closely resembled changes we have previously observed in an animal neuroma model. Local neuropeptides may play a role in the injury response of peripheral nerve, and may be related to mechanosensitivity.
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PMID:Peptides and neuromas: calcitonin gene-related peptide, substance P, and mast cells in a mechanosensitive human sural neuroma. 917 60

The extranuclear endogenous mono-ADP-ribosylation of proteins was monitored in cellular preparations of retina, superior cervical ganglion, dorsal root ganglia and peripheral nerve. At least 6 protein fractions are ADP-ribosylated in the crude extract fraction from retina control preparations, while in diabetic rats the number of retina labeled proteins and the extent of labeling are highly reduced. In the superior cervical ganglion labeling was present in 10 proteins, in diabetics it was greatly decreased. Treatment of diabetic rats with silybin, a flavonoid mono-ADP-ribosyltransferase inhibitor, did not affect hyperglycemia, but prevented the alteration of extent of protein ADP-ribosylation. These data suggest that proteins of retina and peripheral ganglia are excessively ADP-ribosylated in vivo. The effects of silybin treatment on excessive mono-ADP-ribosylation of proteins was associated with the prevention of reduction of substance P-like immunoreactivity levels, that is typical of diabetic neuropathy. In the membrane fraction of sciatic nerve Schwann cells, at least 9 proteins were ADP-ribosylated, diabetes caused a marked increase of labeling. A comparable increase involving the same proteins is triggered by chronic nerve injury and by corticosteroid treatment. Silybin treatment of diabetic rats prevented such an increase. We propose that the inhibition of excessive protein mono-ADP-ribosylation by silybin prevented the onset of diabetic neuropathy. While the effects on Schwann cells is likely indirect and secondary to the improvement of diabetic axonopathy.
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PMID:Endogenous mono-ADP-ribosylation in retina and peripheral nervous system. Effects of diabetes. 919 68

In rodent models of diabetes, there are expression deficits in nerve growth factor (NGF) and in mRNA for its high-affinity receptor, trkA, leading to decreased retrograde axonal transport of NGF and decreased support of NGF-dependent sensory neurons, with reduced expression of their neuropeptides, substance P and calcitonin gene-related peptide (CGRP). Treatment of diabetic rats with intensive insulin normalized these deficits, and treatment with exogenous NGF caused dose-related increases, giving levels of NGF and neuropeptides that were greater than those of controls. Neurotrophin-3 (NT-3) mRNA was also deficient in leg muscle from diabetic rats, and administration of recombinant NT-3 to diabetic rats increased the conduction velocity of sensory nerves without affecting motor conduction velocity. In regenerating nerves after experimental crush injury, expression of NGF in the nerve trunk is increased in diabetes to a greater extent than in controls, but this is offset by a greater reduction in the neuronal expression of trkA in dorsal root ganglia of diabetic rats. Nonetheless, targeted administration of exogenous NGF via impregnated conduits stimulated regeneration in both control and diabetic rats. These findings implicate deficient neurotrophic support in diabetic neuropathy and suggest that its correction should be a paramount therapeutic target.
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PMID:Role of neurotrophins in diabetic neuropathy and treatment with nerve growth factors. 928 98

Untreated streptozotocin-diabetic (7 weeks duration) rats showed reductions (all p < 0.01; percentages in brackets) in motor and sensory nerve conduction velocity (MNCV; 14%, SNCV; 17%) and in sciatic nerve contents of nerve growth factor (NGF; 57%), substance P (SP; 53%) and neuropeptide Y (NPY; 39%). Treatment with a gamma-linolenic acid-alpha-lipoic acid conjugate (GLA-LA; 35 mg x day(-1) x rat(-1)) attenuated (p < 0.05) these reductions to MNCV (8%), SNCV (5%), NGF (19%), SP (23%), NPY (20%), such that the values in GLA-LA-treated diabetic rats did not differ significantly from those of control non-diabetic animals. Treatment with alpha-lipoic acid alone at 100 mg/kg i.p. was without effect on these variables except for NGF (33% reduction, p < 0.05) and treatment with the antioxidant, butylated hydroxytoluene (1.5% dietary supplement) did not affect any deficits. These data show that GLA-LA is effective in improving both electrophysiological and neurochemical correlates of experimental diabetic neuropathy.
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PMID:A lipoic acid-gamma linolenic acid conjugate is effective against multiple indices of experimental diabetic neuropathy. 968 27

A number of functions for nerve growth factor (NGF) have been described over the past years, including its role for neuronal function and regeneration during toxic or metabolic neuropathies. In order to further assess the effects of NGF on the somatosensory system in diabetic neuropathy, the sural nerve, dorsal root ganglia (DRG), and dorsal horn of the spinal cord were investigated by morphological and quantitative methods in rats after 12 weeks of uncontrolled streptozotocin-induced diabetes mellitus. The results from our study suggest a twofold effect of NGF: (1) In sural nerve treatment with NGF (0.1 or 0.5 mg/kg) for 12 weeks was able to reverse distinct diabetes-related alterations in myelinated nerve fiber morphology, such as myelin thickness. These changes occurred in the entire myelinated population of sensory nerves and were not restricted to nociceptive nerve fibers. (2) The NGF effect on neurotransmitters of the sensory, nociceptive system was reflected by increased CGRP and substance P content in the DRG and in the dorsal horn of the spinal cord. No change of trkA receptor immunostaining was seen in DRGs of diabetic rats; however, a reduction of trkA immunoreactivity of DRG neurons was noted after long-term NGF treatment of healthy controls. The data demonstrate that NGF regulates a number of neuronal parameters along peripheral and central parts of the somatosensory pathway in the adult. This neurotrophic support may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy.
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PMID:Nerve growth factor (NGF) and diabetic neuropathy in the rat: morphological investigations of the sural nerve, dorsal root ganglion, and spinal cord. 974 64

Pain management for partial-thickness burns and split-thickness skin graft donor sites remains a persistent problem. Topical capsaicin (trans-b-methyl-N-vanillyl-noneamide) has been successful for pain relief in postherpetic neuralgia, arthritis, and diabetic neuropathy. It is thought to work by inhibiting type C cutaneous factors and by releasing substance P, which is essential for wound healing. To evaluate the effects of topical capsaicin treatment on burn wounds and donor sites, an in vitro study was designed to consider cytotoxic effects of commercial concentrations of capsaicin on keratinocytes and fibroblasts. Human keratinocytes and human fibroblasts were grown in tissue culture and exposed to varying concentrations of capsaicin (0.025% weight/volume to 0.2% weight/volume). In addition, fibroblast-seeded collagen matrixes were exposed to capsaicin to evaluate the compound's ability to cause cytotoxic effects beneath the surface. Keratinocyte growth was reduced 21% to 31% in commercial concentrations of capsaicin 0.025% to 0.20% weight/volume. Fibroblasts were reduced 5% to 10% during the first 6 hours of exposure to capsaicin and 30% after 24 hours across the full range of concentrations tested. At concentrations of at least 0.1% weight/volume, capsaicin penetrated the collagen matrixes, resulting in fibroblast degeneration not only on the surface but also in the inner layers. On the basis of the fact that capsaicin was demonstrated to be cytotoxic to keratinocytes and fibroblasts and on the basis of its known detrimental effect on wound healing, it does not appear that topical capsaicin is indicated for the treatment of burns.
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PMID:Toxic effects of capsaicin on keratinocytes and fibroblasts. 978 76

Morphological and immunohistochemical studies in diabetic subjects have shown a depletion of the neuropeptide substance P (SP) in the central and peripheral nervous system. This is the first study investigating serum levels of substance P in type 1 diabetes patients (n=50) and controls (n=75) by means of an enzyme immunoassay. The serum level of SP was significantly decreased in the diabetic group compared to the control group (10.12+/-0.29 vs. 12.25+/-0.38 pg/ml; p<0.0001). In diabetic patients, there was no correlation of substance P levels with age, serum creatinine, albuminuria, total cholesterol, HDL- or LDL-cholesterol, triglycerides, HbA1c, type or duration of diabetes and gender. Furthermore, there was no difference in serum levels of SP in patients with or without retinopathy, but SP was significantly decreased in patients with neuropathy (9.59+/-0.48 vs. 10.78+/-0.83 pg/ml; p=0.04). These data show that SP is decreased in serum of type 1 diabetes patients, especially in those with diabetic neuropathy. Subsequent and already ongoing prospective studies in well validated diabetic patients with neuropathy may characterize the impact of this neurogenic marker in the course of diabetic neuropathy.
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PMID:Serum levels of substance P are decreased in patients with type 1 diabetes. 1092 10

Topical treatment with capsaicin cream has been shown to be successful in the treatment of different symptomatic nerve disorders like diabetic neuropathy. Conflicting data exist on the effect of capsaicin on nerve function and neurovascular control especially in patients with diabetic neuropathy. The aim of this pilot study was to investigate the impact of topical capsaicin application on small nerve fibre function and neurovascular control. Capsaicin cream was applied to the feet of 13 patients with symptomatic diabetic neuropathy over a period of 8 weeks. Before and during the treatment period, we investigated the total symptoms score, the vibration, thermal (heat and cold) and pain perception thresholds, and the neurovascular responses to heat and acetylcholine stimuli. In addition, the serum plasma levels of substance P, a neurotransmitter of nociceptor C-fibres, were measured. A significant improvement in total symptoms score was observed during topical capsaicin treatment (18.3+/-3.2 vs. 14.3+/-3.3; p<0.05). An improvement in the heat perception threshold was also found (12.7+/-0.4 degrees C vs. 11.4+/-0.7 degrees C: p<0.05), while other sensory nerve fibre functions remained unchanged. No significant change in neurovascular control was observed, neither after mild thermal injury nor after stimulation with acetylcholine. Serum substance P levels increased after initiation of topical capsaicin treatment (72.9+/-5.8 pg/ml vs. 81.7+/-5.0 pg/ml; p<0.05), but returned to baseline levels during further treatment (77.4+/-8.3 pg/ml: n.s.). In conclusion, topical treatment with capsaicin cream over a period of 8 weeks in patients with symptomatic diabetic neuropathy is effective without adverse effects on nerve fibre function or neurovascular control.
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PMID:The influence of local capsaicin treatment on small nerve fibre function and neurovascular control in symptomatic diabetic neuropathy. 1204 33


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