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 flare response in skin largely depends on an intact primary sensory fiber, the C-fiber. We measured the flare response to the intradermal injection of substance P, histamine, and capsaicin in control subjects and in diabetic patients with and without clinically obvious polyneuropathy. The neuropathic diabetic patients had a reduced flare response to substance P, histamine, and capsaicin, compared with control and nonneuropathic diabetic subjects. The smaller flare response in the neuropathic diabetics after capsaicin administration suggested a dysfunction of the peripheral component of the C-fiber. Alternatively, dysfunction of the mast cell or vascular reactivity may contribute to the diminished flare. Because C-fibers participate in nociception in addition to the flare response, the findings of this study, by a method that permits a quantifiable measurement of the function of peripheral sensory neurons in diabetic subjects, has potential usefulness in evaluating sensory neuropathy in diabetic patients.
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PMID:Diminished flare response in neuropathic diabetic patients. Comparison of effects of substance P, histamine, and capsaicin. 244 7

Immunoreactive substance P was determined in lumbar CSF of 35 healthy volunteers and 60 patients with chronic pain syndromes of at least 6 months duration. No significant relationships were found between substance P levels and age, sex or body height. Substance P levels were lower in chronic pain patients, with either neurogenic (n = 23) or idiopathic pain (n = 37) syndromes, than in the healthy volunteers. Substance P levels were especially low in patients with neurogenic pain with lesions involving the extremities and in those with polyneuropathy, while patients with central pain or pain of the head or face had higher values. Substance P levels were related to depressive symptomatology as determined by means of visual analogue scales and to stable personality traits as determined by means of the Karolinska Scales of Personality (KSP). The most consistent (and inverse) relationship was found between substance P levels and the symptom 'inner tension' and between substance P levels and the personality trait 'psychic anxiety.'
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PMID:Substance P in CSF of patients with chronic pain syndromes. 245 41

We have measured substance P-like (SPLI) and somatostatin-like (SLI) immunoreactivities in cerebrospinal fluid of 49 patients with peripheral (polyneuropathy, lumboischialgia) and spinal cord disease and in 16 control patients. The patient groups showed significantly higher CSF SPLI levels than controls while the mean SLI levels were unchanged. Fractionated sampling of CSF (total volume 30 ml) in 20 patients with various neurological diseases showed no significant differences between early and late fractions for SLI. In contrast, lumbar-cisternal concentration gradients were negative for SPLI, total protein and IgG, and positive for the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindolacetic acid. This suggests that SPLI may be released into the lumbar CSF from lower levels of the neuraxis, presumably the spinal cord and spinal ganglia, whereas SLI stems from diffuse CSF secretion without spinal preponderance.
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PMID:Cerebrospinal fluid immunoreactive substance P and somatostatin in neurological patients with peripheral and spinal cord disease. 246 7

Standardised skin biopsies followed by immunohistochemical examination for the presence of terminal nerve fibres reacting for neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) were evaluated. Healthy subjects regularly displayed free nerve endings of both fibre types in the papillary and reticular dermis. Both fibre types were present close to blood vessels, while CGRP immunoreactive fibres were more often encountered near sweat gland acini compared to SP fibres. Diabetes mellitus complicated by polyneuropathy was accompanied by marked reduction of SP and CGRP reactive fibres in the dermis layers. Five type I diabetes patients without clinical or neurophysiological evidence of polyneuropathy also had reduced density of both fibre types, being significant for CGRP fibres when compared with controls. Skin biopsy with immunohistochemical staining for neuropeptides may represent a sensitive tool in evaluation of patients with peripheral neuropathies.
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PMID:Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus. 248 Apr

The widespread cutaneous vasodilation which can be induced by low-frequency transcutaneous nerve stimulation (TNS) in humans is, at least in part, due to sympatho-inhibition. Studies on the additional involvement of an active local vasodilator have demonstrated a moderate increase in plasma vasoactive intestinal polypeptide (VIP) but excluded a series of known dilators. In the present study sera from four patients with peripheral ischaemia (three with Raynaud's disease, and one with diabetic polyneuropathy) were assayed for vasoactivity on isolated vascular smooth muscle (rat portal vein) with reactivity towards a wide series of classical neurotransmitters and neuropeptides. In the presence of cholinergic and beta-adrenergic blockade sera collected after TNS-induced vasodilation revealed an inhibitory activity which could not be accounted for by changes in osmolarity, pH or K+. The inhibitory response to the plasma samples developed more rapidly than the response to synthetic VIP. The inhibitory activity of the plasma samples excluded a series of other peptides such as substance P, neurotensin, pancreatic polypeptide, bradykinin and angiotensin II, which all enhanced the contractile activity in the rat portal vein. There was a proportional increase in skin temperature and occurrence of inhibitory activity in cubital plasma samples in response to TNS. The results suggest that a peripheral vasodilator activity besides VIP may be implicated in the sustained dilation induced by TNS in these patients.
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PMID:In search of mediators of skin vasodilation induced by transcutaneous nerve stimulation: IV. In vitro bioassay of the vasoinhibitory activity of sera from patients suffering from peripheral ischaemia. 671 38

1. Lumbar spinal substance P and calcitonin-gene-related peptide derive from spillage out of the dorsal horns associated with activity of small primary sensory afferents (C- and A delta-fibres). Cerebrospinal fluid and sural nerve levels of substance P and calcitonin-gene-related peptide have been measured in patients with diabetic polyneuropathy to determine whether differences in small primary sensory afferent activity are related to the presence or absence of painful symptoms. 2. Calcitonin-gene-related peptide was undetectable in the cerebrospinal fluid of the majority of diabetic patients (14 out of 22); it was lower overall in diabetic patients as compared with control subjects (P < 0.01), it was lower in those diabetic patients with painless neuropathy (100% undetectable) as compared with those with painful neuropathy (50% undetectable; P < 0.05) and it correlated conversely with warming threshold (r = 0.50; P < 0.01). 3. Substance P showed no overall numerical intergroup differences or correlation with other measured variables, but six diabetic patients as compared with one control subject had undetectable cerebrospinal fluid levels and the proportion of patients with undetectable levels was higher in the group with painless neuropathy than in the group with painful neuropathy (P < 0.05). 4. The levels of each peptide in cerebrospinal fluid correlated with its equivalent in sural nerve (P < 0.01 for calcitonin-gene-related peptide and P < 0.03 for substance P). Calcitonin-gene-related peptide correlated with substance P in the sural nerve (r = 0.84; P < 0.002) and in the cerebrospinal fluid (r = 0.30; P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebrospinal fluid levels of substance P and calcitonin-gene-related peptide: correlation with sural nerve levels and neuropathic signs in sensory diabetic polyneuropathy. 768 39

Nerve growth factor (NGF) is trophic to sensory and sympathetic fibers. In animal models, NGF is depleted in diabetic nerves and NGF deprivation produces hypoalgesia. Exogenous NGF can reverse some of the pathological changes in diabetic nerves and NGF excess leads to hyperalgesia. We have quantified sensory and autonomic function in early diabetic polyneuropathy and correlated changes with levels of NGF and neuropeptides in affected skin. We describe an early length-dependent dysfunction of sensory small-diameter fibers, prior to dysfunction of sympathetic fibers, with depletion of skin NGF and the sensory neuropeptide substance P. We describe a significant correlation between NGF depletion and decreased skin axon-reflex vasodilation, mediated by small sensory fibers partly via substance P release. Immunostaining shows depletion of NGF in keratinocytes in diabetic skin. We propose that a decrease in endogenous skin-derived NGF influences the presentation of diabetic polyneuropathy, although metabolic or vascular abnormalities may be the cause of the neuropathy. As loss of nociception and axon-reflex vasodilation contribute to diabetic foot ulceration, early and prolonged NGF treatment at an appropriate dose may provide rational prophylaxis for this condition.
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PMID:The role of endogenous nerve growth factor in human diabetic neuropathy. 864 May 66

Substance P is one of the neurotransmitters released by primary nociceptive neurons in the dorsal horn of the spinal cord and it binds postsynaptically to NK(1)-receptors. This receptor is therefore an obvious target for analgesic drugs. The aim of this multicenter, randomised, double-blind, placebo-controlled and parallel-group study was to test if the non-peptide NK(1)-receptor antagonist TKA731 would relieve painful diabetic polyneuropathy. Eighty-seven patients completed a treatment period of 2 weeks' duration with TKA731 (150 mg daily) or placebo preceded by one week for baseline observations. There was no significant difference between TKA731 and placebo in change in pain rating from baseline to study end neither for rating of total pain (mean -13.4 mm vs. -11.6 mm, p = 0.664) nor for change in ratings of different pain symptoms (touch- or pressure-evoked pain, pain paroxysms, steady burning or deep aching pain) (p = 0.169-0.834).
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PMID:The NK1-receptor antagonist TKA731 in painful diabetic neuropathy: a randomised, controlled trial. 1619 88

Several groups have reported apoptosis of dorsal root ganglion (DRG) cells as a prominent feature of diabetic polyneuropathy (DPN), although this has been controversial. Here, we examined subacute (4-month) type 1 diabetic BB/Wor rats with respect to sensory nerve functions, DRG and sural nerve morphometry, pro- and antiapoptotic proteins, and the expression of neurotrophic factors and their receptors. Sensory nerve conduction velocity was reduced by 13% and was accompanied by significant hyperalgesia. The numbers of DRG neurons including substance P-and calcitonin gene-related peptide-positive neurons were not altered, although they showed significant atrophy. Sural nerve morphometry showed decreased numbers of myelinated and unmyelinated fibers. Active caspase-3 and Bax expressions were increased, whereas antiapoptotic Bcl-xl and heat shock protein (HSP) 27 expressions in DRGs were increased. Nerve growth factor (NGF) contents in sciatic nerves and the expression of NGF receptor TrkA in DRGs were decreased. Immunohistochemistry showed increased numbers of active caspase-3-, HSP70-, and HSP27-positive neurons. Examinations of DRGs revealed no structural evidence of apoptosis but rather progressive hydropic degenerative changes. We conclude that apoptotic stress is induced in DRGs but is counterbalanced by survival elements in subacute type 1 diabetic BB/Wor rats and that distal nerve fiber loss reflects a dying-back phenomenon caused by impaired neurotrophic support.
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PMID:Apoptotic stress is counterbalanced by survival elements preventing programmed cell death of dorsal root ganglions in subacute type 1 diabetic BB/Wor rats. 1624 57

DNA microarray analysis is a powerful tool for simultaneous analysis and comparison of gene products expressed in normal and diseased tissues. We used this technique to identify differentially expressed genes (DEGs) in nerve biopsy samples of chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VAS) patients. We found novel previously uncharacterized genes of relevance to CIDP or VAS pathogenesis. Of particular interest in CIDP were tachykinin precursor 1, which may be involved in pain mediation, stearoyl-co-enzyme A (CoA) desaturase, which may be a marker for remyelination, HLA-DQB1, CD69, an early T-cell activation gene, MSR1, a macrophage scavenger receptor, and PDZ and LIM domain 5 (PDLIM5), a factor regulating nuclear factor (NF)-kappa B activity. Genes upregulated in VAS included IGLJ3, IGHG3, IGKC, and IGL, which all function in B-cell selection or antigen recognition of B cells. Other upregulated genes included chemokines, such as CXCL9 and CCR2, as well as CPA3, a mast cell carboxypeptidase. Allograft inflammatory factor-1 (AIF-1), a modulator of immune response was upregulated both in CIDP and VAS. Microarray-based analysis of human sural nerve biopsies showed distinct gene expression patterns in CIDP and VAS. DEGs might provide clues to the pathogenesis of the diseases and be potential targets for therapeutics.
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PMID:Differential gene expression in nerve biopsies of inflammatory neuropathies. 2169 94


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