Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simultaneous visualization of nerves and mast cells in the rat synovium was possible with double staining. Thus, a direct comparison could be made of nerves and mast cells in the ankle joints of healthy rats and in those with severe adjuvant induced polyarthritis. Nerves were studied with avidin-biotin-peroxidase complex (ABC) immunostaining, using heterologous antisera to protein gene product 9.5 (PGP 9.5), a recently discovered neural protein, and the neuropeptides substance P and calcitonin gene related peptide (CGRP). Mast cells were visualized by metachromatic staining of granule heparin. With double staining of sections, a parallel distribution of mast cells and nerves in all parts of the normal synovium was noted. In rats with adjuvant induced arthritis, a near total parallel disappearance of mast cells and nerves in the synovium occurred. In the arthritic rat such mast cell/nerve "units" were only present in the region where synovium attaches to bone. The observed regional depletion of both nerves and mast cells in arthritis may be of importance in the pathophysiology of arthritis.
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PMID:Regional distribution of mast cells and peptide containing nerves in normal and adjuvant arthritic rat synovium. 170 28

The distribution of peptides thought to be involved in pain modulation--substance P, calcitonin gene-related peptide (CGRP), and enkephalin--were studied in the spinal cord and dorsal root ganglia of polyarthritic rats and in rats with one sciatic nerve sectioned prior to induction of arthritis. In arthritic rats there was a bilateral increase of CGRP- and substance P-immunoreactive fibers and appearance of enkephalin-immunoreactive cell bodies in the dorsal horn of the lumbar (L4) spinal cord when compared to controls. In the corresponding dorsal root ganglia there were significant increases of CGRP- (P less than 0.02) and substance P- (P less than 0.001) immunoreactive cell bodies compared to controls. In the ventral horn of the control rats CGRP-immunoreactive motoneurons were abundant but were significantly (P less than 0.001) reduced in the arthritic spinal cord. Less pronounced changes were seen in the contralateral L4 spinal cord of arthritic rats with unilateral sciatic nerve section. In the ipsilateral dorsal horn, however, CGRP- and substance P-immunoreactive fibers were markedly depleted, and no enkephalin cell bodies were present. Furthermore, a number of CGRP-immunoreactive motoneurons were observed. In the ipsilateral L4 ganglia CGRP- (P less than 0.02) and substance P- (P less than 0.02) immunoreactive cells were significantly decreased compared to the contralateral side. The data suggest that pain perception is linked to complex interactions between CGRP, substance P, and enkephalin in sensory pathways and an intact peripheral input. The loss of CGRP-immunoreactive motoneurons may reflect muscular dysfunction associated with the arthritic condition.
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PMID:Increased calcitonin gene-related peptide (CGRP), substance P, and enkephalin immunoreactivities in dorsal spinal cord and loss of CGRP-immunoreactive motoneurons in arthritic rats depend on intact peripheral nerve supply. 171 33

There is evidence that neuropeptides play a role in the development of arthritis. Synovial fluid from arthritic temporomandibular joints in patients with rheumatoid arthritis was therefore investigated for presence of the neuropeptides calcitonin gene-related peptide, substance P, neurokinin A and neuropeptide Y. All four peptides were found in the synovial fluid above plasma level, but calcitonin gene-related peptide showed the highest concentration and substance P the lowest.
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PMID:Neuropeptides in temporomandibular joints with rheumatoid arthritis: a clinical study. 172 47

We have studied the presence of five neuropeptides in knee joint synovial fluid from either patients suffering from rheumatoid arthritis and pain (n = 18) or being subjected to arthroscopy due to meniscal/cruciate ligament injuries (n = 13). Radioimmunoassay technique was used for peptide analysis using antisera SP2 against substance P (SP), K12 against neurokinin A (NKA), CGRPR8 against calcitonin gene-related peptide (CGRP), NPY1 against neuropeptide Y (NPY) and VIP2 against vasoactive intestinal polypeptide (VIP). No SP could be detected, and lower levels of NKA was found in arthritic joints vs controls. CGRP and NPY was found in higher concentrations in arthritic patients vs controls. VIP was found sporadically in both arthritis and control patients. Our data show some quantitative differences between patients suffering rheumatoid arthritis and pain, and patients with non-inflamed joints without pain; indicating an involvement of peptidergic fibers in arthritis in humans.
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PMID:Concentration of substance P, neurokinin A, calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide in synovial fluid from knee joints in patients suffering from rheumatoid arthritis. 194 95

This immunohistochemical study of nerves in the synovial tissue of Sprague-Dawley rats demonstrated the occurrence of 4 neuropeptides and 2 enzymes that are involved in the synthesis of catecholamines. Substance P and calcitonin gene-related peptide were colocalized in fibers that terminated as varicosal endings in the synoviocyte layer. Similarly, tyrosine hydroxylase and dopamine beta-hydroxylase, which reflect the presence of noradrenaline, were colocalized with neuropeptide Y. These fibers were predominantly found adjacent to and within blood vessel walls. Immunoreactivity to vasoactive intestinal polypeptide was seen in varicose nerve terminals in the synoviocyte layer. Many were localized in vessel walls. There is accumulating evidence of an involvement of substance P and noradrenaline in the pathogenesis of inflammatory joint disease and nociception. The role of these colocalized neuropeptides, namely, calcitonin gene-related peptide and neuropeptide Y, in the pathophysiology of such conditions warrants further analysis.
Arthritis Rheum 1990 Jun
PMID:Noradrenergic and peptidergic nerves in the synovial membrane of the Sprague-Dawley rat. 197 38

Rheumatoid arthritis is associated with both localized and generalized osteoporosis. Localized osteoporosis can be considered to be caused by local disease mechanisms, including the generation of factors from activation of the cytokine pathway. The etiology of generalized osteoporosis has been difficult to elucidate, particularly because of the lack of sensitive techniques to measure bone mineral density. The introduction of single- and dual-photon absorptiometry and quantitative computed tomography has allowed more accurate assessment of bone mineral density. In general, bone mineral density loss at appendicular sites does not correlate well with axial bone density loss. Corticosteroid treatment exaggerates the development of osteoporosis in up to 40% of patients with rheumatoid arthritis. Sex hormone status, physical activity, disease duration, and functional class are all significant predictors for the development of osteoporosis. Current therapy for prevention and treatment is based largely on theoretical considerations. Physical activity should be encouraged once acute joint inflammation has settled. Postmenopausal women and amenorrheic premenopausal women will benefit from cyclical estrogen replacement. Patients with low serum 1,25-dihydroxy vitamin D3 levels, and males with low serum testosterone levels, are candidates for replacement therapy with the appropriate hormones. In patients who are receiving corticosteroids the dose should be limited, and oral calcium supplements are of benefit. The use of the newer corticosteroid deflazacort, and disease-modifying immunosuppressive drugs, are discussed. Other therapeutic options which should be considered, although published trials are scarce, are calcitonin and the diphosphonates. Further studies are awaited concerning the optimum prevention and treatment of osteoporosis associated with rheumatoid arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)
Semin Arthritis Rheum 1991 Feb
PMID:Osteoporosis associated with rheumatoid arthritis: pathogenesis and management. 204 57

The influence of circulating antibodies to calcitonin gene-related peptide on the inflammatory response was examined in rats with adjuvant-induced arthritis. Rats were immunized with alpha calcitonin gene-related peptide conjugated to thyroglobulin, and circulating antibodies were identified by their capacity to bind radiolabelled rat alpha or human calcitonin gene-related peptide. In unimmunized rats and rats immunized with thyroglobulin alone, the secondary lesions (characterized as paw swelling, nodules on ears and tail, and inflamed nose) produced after adjuvant-induced arthritis were similar. However, at 21 days, when these lesions were maximal, the animals immunized with calcitonin gene-related peptide showed decreased numbers of lesions. An additional marker of disease activity, namely alpha 1 glycoprotein levels in plasma, was also measured. Again, plasma alpha 1 glycoprotein levels were similar in rats that were unimmunized or received thyroglobulin alone, but at 21 days were significantly reduced in animals immunized with calcitonin gene-related peptide. In contrast, the initial foot swelling seen in the first few days after injection of adjuvant was not significantly different in the various groups. The results suggest that antibodies to calcitonin gene-related peptide are able to reduce the severity of the adjuvant arthritis syndrome, and that this peptide contributes to the inflammatory response seen in the later stages of the disease model.
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PMID:Immunization with calcitonin gene-related peptide reduces the inflammatory response to adjuvant arthritis in the rat. 212 53

The influence of adjuvant-induced arthritis of the rat on central and peripheral peptide neuroanatomy was investigated by immunohistochemistry. The most striking feature of arthritic rats was the differential intensification of neuronal proenkephalin- and prodynorphin-related staining in dorsal horn. Changes were ipsilateral in monoarthritic and bilateral in polyarthritic rats as compared to controls. Opioid responsive neurons were target of substance P (SP) and calcitonin gene-related peptide (CGRP) fibers. Changes of SP and CGRP predominated in peripheral inflamed tissue and consisted of intensified immunostaining and an apparent sprouting of sensory fibers particularly around venules, in the epidermis and in areas infiltrated by immunocompetent cells. Opioid staining was absent from primary afferents but present in some immune cells of inflamed tissue. Endogenous antinociceptive opioids and pro-nociceptive/pro-inflammatory SP and CGRP may be crucial in the concerted response of the neuroimmune system to chronic inflammatory pain.
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PMID:Peptide neuroanatomy of adjuvant-induced arthritic inflammation in rat. 246 72

We examined the effect of adjuvant arthritis on the content of immunoreactive calcitonin gene-related peptide (iCGRP) in the dorsal root ganglia at L4-L6 levels and the spinal cord at a lumbar level in rats. Arthritis was induced by inoculating adjuvant into both hind-paws twice at a 10 day interval. In the arthritic rats 15 days after the first inoculation (day 15), the content of iCGRP was significantly increased in the dorsal root ganglia, with no change in the dorsal and ventral horns. The content in the dorsal root ganglia was still high on day 26 and had decreased by day 40. An intrathecal injection of colchicine (0.2 mg, 18 hr before killing) enhanced the increase of iCGRP in the dorsal root ganglia and decreased it in the dorsal horn of arthritic rats, although in noninoculated rats such treatment produced no significant changes in the content of iCGRP in both regions. The arthritis-induced increase in the content of iCGRP in the dorsal root ganglia was significantly reduced after treatment with the antiinflammatory analgesic, diclofenac sodium, in a dose of 3 mg/kg/day, PO for 10 days. Swelling and hyperalgesia in the hind-paw were depressed after such treatment. These results suggest that adjuvant arthritis with long-lasting inflammation with pain facilitates the turnover, especially biosynthesis, of CGRP in primary afferent neurons.
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PMID:Calcitonin gene-related peptide increases in the dorsal root ganglia of adjuvant arthritic rat. 278 10

We have analysed the concentrations of substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in the synovial fluid from 5 patients suffering from arthritis with inflamed knee joints as well as from 5 healthy control subjects with an earlier traumatic meniscal or cruciate ligament injury. Competitive radioimmunoassay was done using antisera SP2 (SP), K12 (NKA), R8 (CGRP), and NPY1 (NPY). No SP-like immunoreactivity (-LI) was detected in any patient. NKA-LI was found in all control patients but in none of the arthritis patients. CGRP-LI was seen in all arthritis patients as well as in 3/5 control patients, a non-significant difference. NPY-LI was found in a significantly higher concentration in the arthritis group vs the control patients. The results support an involvement of neuropeptides in human joint inflammation.
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PMID:Immunoreactive tachykinins, calcitonin gene-related peptide and neuropeptide Y in human synovial fluid from inflamed knee joints. 278 54


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