Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synovial tissue was obtained from medial, lateral, and suprapatellar sites of 21 knees (15 patients) with medial compartmental osteoarthritis at surgery. All patients reported pain around the medial joint of their knees while walking and climbing stairs. For investigation of the synovial innervation, six samples were stained with modified gold chloride and the others with an immunohistochemical method using antisera against neuropeptides. The extent of synovitis in each part was scored using a new 10-point scale. The results showed that the synovium had an extensive neural network in the somatic and autonomic nervous systems. Neuropeptides were most abundant, with an especially large number of substance P and calcitonin gene related peptide immunoreactive free nerve endings. Some of the substance P positive nerve endings were surrounded by monocytes. Substance P and calcitonin gene related peptide were found more frequently in the medial than in the lateral or suprapatellar areas. Substance P positive free nerve endings showed more dendritic morphologic features in the medial region than did those in the lateral and suprapatellar regions, and small nerves were accompanied by newly developed vessels in synovial villi. In the medial region, the synovitis was more remarkable than in the lateral region. These findings suggest that free nerve endings containing substance P may modulate inflammation and the pain pathway in osteoarthritis.
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PMID:Distribution of neuropeptides in synovium of the knee with osteoarthritis. 1090 73

Our objective was to investigate sympathetic and sensory nerve fibers in synovial tissue in rheumatoid arthritis (RA) and osteoarthritis (OA) in relation to histological inflammation and synovial cytokine and norepinephrine (NE) secretion. Immunohistochemistry was used to detect nerve fibers and inflammatory parameters. A superfusion technique of synovial tissue pieces was used to investigate cytokine and NE secretion. In RA, we detected 0.2 +/- 0.04 tyrosine hydroxylase-positive (TH-positive=sympathetic) nerve fibers/mm2 as compared to 4.4 +/- 0. 8 nerve fibers/mm2 in OA (P<0.001). In RA, there was a negative correlation between the number of TH-positive nerve fibers and inflammation index (RRank=-0.705, P=0.002) and synovial IL-6 secretion (RRank=-0.630, P=0.009), which was not found in OA. Substance P-positive (=sensory) nerve fibers were increased in RA as compared to OA (3.5+/-0.2 vs. 2.3+/-0.3/mm2, P=0.009). Despite lower numbers of sympathetic nerve fibers in RA than in OA, NE release was similar at baseline (RA vs. OA: 152+/-36 vs. 106+/-21 pg/ml, n.s.). Basal synovial NE secretions correlate with the number of TH-positive CD 163+ synovial macrophages (RA: RRank=0.622, P=0.031; OA: RRank=0.299, n.s.), and synovial macrophages have been shown to produce NE in vitro. Whereas sympathetic innervation is reduced, sensory innervation is increased in the synovium from patients with longstanding RA when compared to the synovium from OA patients. The differential patterns of innervation are dependent on the severity of the inflammation. However, NE secretion from the synovial tissue is maintained by synovial macrophages. This demonstrates a loss of the influence of the sympathetic nervous system on the inflammation, accompanied by an up-regulation of the sensory inputs into the joint, which may contribute to the maintenance of the disease.
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PMID:The loss of sympathetic nerve fibers in the synovial tissue of patients with rheumatoid arthritis is accompanied by increased norepinephrine release from synovial macrophages. 1102 94

In a pilot study, the action of the 5-HT3 receptor antagonist, tropisetron, on different types of local rheumatic pain and inflammatory effects was studied. With intra-articular injection of tropisetron, an improvement in inflammation and pain was obtained in inflammatory rheumatic diseases and activated osteoarthrosis. Also, the majority of patients with localized soft-tissue rheumatic diseases (periarthritis) demonstrated an obvious decrease in their pain following local infiltration of tropisetron. Chronic low back pain and cervical pain responded somewhat to i.v. treatment with tropisetron. The effect of the 5-HT3 receptor antagonists is probable primarily to limit the release of substance P, which acts as a pain and inflammatory mediator, and is itself released by the neurogenic inflammation that occurs after the binding of serotonin to its corresponding receptor. These results should be backed up with placebo controlled studies, which if confirmed, might imply that 5-HT3 receptor antagonists could supplement or replace the local administration of corticosteroids.
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PMID:The use of 5-HT3 receptor antagonists in various rheumatic diseases--a clue to the mechanism of action of these agents in fibromyalgia? 1102 36

We examined the production of substance P (SP) in synovial fibroblasts derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunoreactive SP was observed in non-stimulated RA fibroblasts. The expression of beta-preprotachykinin-A (beta-PPT-A) mRNA was confirmed by reverse transcription-polymerase chain reaction analysis. SP contents in culture medium were increased by treatment of RA fibroblasts with transforming growth factor-beta (TGFbeta) (10 ng/ml). Levels of SP release were elevated at 12 h after TGFbeta stimulation whereas the expression of beta-PPT-A mRNA was enhanced at 3 h. Furthermore, SP production in response to TGFbeta was dose-dependently enhanced by basic fibroblast growth factor (bFGF). OA fibroblasts also significantly released SP in the presence of TGFbeta (10 ng/ml) plus bFGF (50 ng/ml). These results suggest that SP produced by synovial fibroblasts may participate in joint diseases.
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PMID:Production of neuropeptide substance P by synovial fibroblasts from patients with rheumatoid arthritis and osteoarthritis. 1132 7

Topically applied capsaicin (CAS 404-86-4) induces the release of substance P, a neurotransmitter, from sensory C-fibres. In addition, there is a specific blockade of transport and de-novo synthesis of substance P. As a result, repeated applications of capsaicin bring about a long lasting desensitisation to pain (increase of pain threshold). The desensitising effect is fully reversible. The confirmed pharmacodynamic actions and a number of double-blind clinical studies indicate that local capsicum preparations are very suitable for the treatment of neuropathic pain or musculoskeletal disorders, with or without inflammatory components. In a double-blind, randomised parallel-group study a capsicum plaster was compared with a placebo for 3 weeks in 154 patients with non-specific back pain. Inclusion criteria were a history of back pain for a minimum period of 3 months and a degree of pain of 5 or more on an eleven grade visual analogue scale. The principal target variable consisted of the score of 3 combined pain scales. Secondary efficacy measures were tests of mobility, a disability index (in the context of Arhus low back rating scale) and global assessments by physicians and patients. For patients to be rated as responders their total pain score at the final examination after 3 weeks of treatment had to show a reduction by at least 30% of the baseline value. The study unequivocally achieved the target criterion with a rate of responders in the capsicum group of 60.8% against 42.1% in the placebo group (p = 0.0219). The sum of the 3 separate pain scales decreased more markedly in the capsicum group than in the placebo group (38.5% compared to 28.0%; p = 0.002). Relatively slight improvements of the impaired mobility and the functional status are explained by the characteristics of the disorder treated. The efficacy ratings by observers and patients was definitely in favour of capsicum. Adverse effects--mostly harmless and resolving spontaneously--were reported by 15 patients in the capsicum group and by 9 in the placebo group. The tolerance ratings by investigators and patients were superior to the placebo product. This, however, partly is due to the local pharmacological actions of the drug. As in comparably positive randomised studies with capsaicin cream in patients with osteoarthritis or fibromyalgia it was shown that a capsicum plaster preparation can also be used to advantage in chronic non-specific back pain.
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PMID:Capsicum pain plaster in chronic non-specific low back pain. 1176 91

Previous work has shown a progressive, age-related loss of knee joint innervation in the C57BL6Nia mouse. We did three experiments to describe further the loss and determine whether it might contribute to the development of knee osteoarthrosis in this model. Immunocytochemistry showed that the percentage of neurons expressing substance P and calcitonin gene-related peptide increased with age, indicating a relatively selective loss of mechanoreceptors. Histological examination of knee joints of mice at various ages showed that loss of joint innervation always preceded histological changes of cartilage degeneration. The mice usually developed a mild form of osteoarthrosis, but surgical ablation of joint innervation caused the development of severe patellofemoral osteoarthrosis. The findings are consistent with the hypothesis that an age-related loss of joint innervation may contribute to the development of osteoarthrosis.
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PMID:Evidence for a neuropathic contribution to the development of spontaneous knee osteoarthrosis in a mouse model. 1192 17

In the present study, we have investigated the in vitro effect of calcitonin-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and vasoactive intestinal peptide (VIP) at concentrations of 10(-8), 10(-9) and 10(-10) M on the production of different proinflammatory cytokines or chemokines such as IL-1beta, IL-6 and TNFalpha by peripheral whole blood cells from patients with rheumatoid arthritis, as well as from osteoarthritis patients studied as a control group without immunoinflammatory background. We have found that CGRP, NPY, SP and VIP stimulated significantly the production of those cytokines and chemokines in rheumatoid arthritis patients. In general, the stimulation was higher at the 10(-9) M concentration, with SP and VIP, and in rheumatoid arthritis patients compared to osteoarthritis ones. Neuropeptides did not significantly modify the LPS-induced cytokine production by whole blood cells. The results indicate that physiological concentrations of the neuropeptides studied can modulate the inflammatory and immunological response, stimulating significantly the production of inflammatory cytokines by human whole blood cells in rheumatoid arthritis patients, as well as, in a minor way, in osteoarthritis patients.
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PMID:Effect of calcitonin gene-related peptide, neuropeptide Y, substance P, and vasoactive intestinal peptide on interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha production by peripheral whole blood cells from rheumatoid arthritis and osteoarthritis patients. 1287 94

Both the analgesic drugs tramadol and paracetamol are widely used for the symptomatic therapy of osteoarthritis (OA). The aim of this double-blind, randomised study in patients with knee OA was to compare their effects on synovial fluid concentrations of interleukin (IL)-6 and substance P (SP). Moreover, we evaluated plasma and synovial fluid concentrations of tramadol and its active metabolite (O-desmethyl-tramadol, M1) after oral treatment with this drug. Twenty patients were enrolled. A group of 10 patients received tramadol (50 mg three times a day), and another group of 10 patients were treated with paracetamol (500 mg three times a day) for 7 days. Both drugs significantly reduced the intensity of joint pain. The synovial fluid concentrations of SP were significantly reduced only by the treatment with tramadol. In this group of patients, IL-6 synovial fluid concentrations were slightly, but not significantly, decreased. Paracetamol did not significantly change the synovial fluid concentrations of SP and IL-6. After oral administration, a considerable amount of tramadol was measurable in synovial fluid. Both in plasma and synovial fluid the concentrations of M1 were markedly lower than those of tramadol, with a T/M1 ratio of 14.7+/-4.6 and 9.3+/-3.9, respectively. These data demonstrate that the activity of tramadol may involve the modulation of inflammatory mediators. Moreover, they indicate that after oral treatment with tramadol, both the parent drug and its active metabolite can penetrate into synovial fluid.
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PMID:Effects of tramadol on synovial fluid concentrations of substance P and interleukin-6 in patients with knee osteoarthritis: comparison with paracetamol. 1463 39

Substance P (SP) and calcitonin gene-related peptide (CGRP) have been found in the perichondrium and within the cartilage canals. It is still unknown whether they exert a direct effect on chondrocytes during joint development. We processed 28 knees of newborn Wistar rats in 7 different fashions to perform histology and immunohistochemistry studies. Positive immunoreactivity against CGRP and SP was found in the inner aspect of the perichondrium in a close contact with chondrocytes. The presence of CGRP and SP indicates the presence of nerves fibers, and precedes the development of cartilage canals. Nerve fibers may play a role in the development of synovial joints before and during the presence of cartilage canals. The presence of CGRP and SP in the cartilage at birth may be involved in the early postnatal maturation of synovial joints. It remains to be determined whether autonomic innervation is later involved in age-related degenerative joint disease.
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PMID:Immunohistochemical localization of calcitonin gene-related peptide and substance P in the rat knee cartilage at birth. 1623 69

The objective of the study was to evaluate the distribution of substance P-immunoreactive nerve fibers in osteoarthritis knee and to determine whether a degenerative disease has any influence on the occurrence of neuropeptide-containing fibers, positively stained for substance P. Twenty consecutive patients, 16 females and 4 males, with gonarthrosis participated in the study. For comparison we used the group of 20 patients, 14 females and 6 males, operated on because of traumatic lesion of the knee. The medial and lateral retinaculum, medial compartment synovium and infrapatellar fat pad of these two groups of patients were evaluated using monoclonal antibody to substance P (PEPA40, Serotec Ltd, UK). The slices were examined semi-quantitatively for nerve fibers showing substance P expression. The values were analyzed with ONE WAY ANOVA test, which was then corrected with LSD test, at the level of significance p<0.05. There were no statistical differences in distribution of substance P nerve fibers in the fat pad, lateral and medial retinaculum or synovium between both groups, as well as in the each study group (p<0.05). The results allow us to speculate that different biomechanical axial disturbances of the knee could have the same influence on substance P-positive mechanoreceptors of the soft tissues around the joint modulating the pain pathway in knee osteoarthrosis.
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PMID:Distribution of substance P nerve fibers in osteoarthritis knee joint. 1647 80


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