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)

During the initial months of long-term treatment of Paget's disease of bone with salmon calcitonin, circulating alkaline phosphatase activity and urinary hydroxyproproline excretion usually decrease by about 50%. In 22 of 85 patients these parameters returned to pretreatment levels despite continuous therapy. Nineteen patients who were resistant to salmon calcitonin had salmon calcitonin antibodies in high titer. Human calcitonin has been effective in suppressing disease activity in these patients. The pathogenesis of calcitonin resistance in patients without antibodies is unknown.
Arthritis Rheum 1980 Oct
PMID:Salmon calcitonin therapy for Paget's disease of bone. The problem of acquired clinical resistance. 700 81

Previous reports have demonstrated suppressive effects of salmon calcitonin (SCT) on inflammation and immune reactions. A rat model of arthritis induced by immunization with type II collagen was studied in an attempt to demonstrate antirheumatic and immunosuppressive actions of SCT. No inhibition of arthritis or of specific immune responses to collagen was found.
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PMID:Failure of calcitonin to inhibit collagen-induced arthritis in rats. 716 38

The chemistry and physiology of calcitonin are reviewed with particular emphasis on the evolution of the hormone and its modern role in humans. It seems likely that the relative deficiency of calcitonin in women may be important in postmenopausal bone loss. A major therapeutic application of calcitonin is in the treatment of Paget's disease of bone, and current recommendations for therapy are presented.
Arthritis Rheum 1980 Oct
PMID:Chemistry, physiology, and therapeutic applications of calcitonin. 719 7

1. Many experimental and clinical arthritides are characterized by their bilateral nature. There is strong evidence to suggest that this bilateral spread may be mediated by a neuronal mechanism. We have previously shown early and sustained induction of mRNAs encoding preprotachykinin (PPT) and calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons innervating an inflamed, arthritic joint. We have now investigated the involvement of capsaicin-sensitive primary afferents and the expression of neuropeptide mRNAs in the maintenance and bilateral spread of mild adjuvant-induced arthritis in the rat. 2. Capsaicin was applied perineurally to either the left (Cap-L) or right (Cap-R) sciatic nerve of halothane-anaesthetized male Han Wistar rats. Two weeks after capsaicin lesioning, arthritis was induced by injection of Freund's complete adjuvant (FCA) around the left ankle at a dose that caused inflammation of the left ankle joint, and a delayed (14 days) contralateral (right) ankle arthritis. Arthritis was monitored for 15 days after injection, when animals were killed and the lumbar DRG dissected. PPT, CGRP, somatostatin (SS), and vasoactive intestinal polypeptide (VIP) mRNA expression was determined in L5 DRG using in situ hybridization. 3. Spread of inflammation/arthritis to the right limb was associated with bilateral rises in PPT and CGRP mRNA expression in L5 DRG. SS mRNA expression in right DRG was unaffected by spread of inflammation. FCA-L+Cap-L reduced left joint swelling and prevented spread of arthritis to the right joint when assessed by joint swelling. This inhibition of spread of arthritis was associated with significant reductions in all left L5 DRG neuropeptide mRNAs compared with controls, and the rise in right L5 DRG PPT mRNA expression seen in FCA-L-alone animals was blocked. FCA-L+Cap-R also reduced left joint swelling and prevented the spread of inflammation to the right ankle. This lesion prevented the rise in PPT and CGRP mRNA expression seen in right DRG with FCA-L alone. 4. These findings suggest a role for capsaicin-sensitive primary afferents and the primary afferent neuropeptides encoded by PPT and CGRP mRNA in the maintenance and spread of arthritis.
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PMID:Neuropeptide gene expression and capsaicin-sensitive primary afferents: maintenance and spread of adjuvant arthritis in the rat. 747 11

The occurrence of substance P (SP) and calcitonin gene-related peptide (CGRP) was assessed in the ankle joints and dorsal root ganglia (L2-L6) by immunohistochemistry and radioimmunoassay (RIA) after unilateral sciatic nerve section in adjuvant arthritis. Nerve section in arthritic rats had no clear-cut effect on warmth, redness, and swelling of ankle joints, but significantly affected the occurrence of SP and CGRP. Immunohistochemical analysis showed an almost complete disappearance of SP-positive fibers in the ipsilateral ankle joint in normal rats after axotomy, whereas in arthritic rats occasional SP-positive fibers remained. In dorsal root ganglia, only occasional SP-positive cells could be detected in normal and arthritic rats after axotomy. A similar but somewhat less pronounced effect of axotomy was noted for neuronal CGRP-LI. RIA showed a decrease in SP in ankle joints by 45% in normal rats and 58% in arthritic rats; the decrease in CGRP was 41% and 47%, respectively. In dorsal root ganglia, the decrease in SP after surgical denervation was 25% in normal rats and 54% in arthritic rats; the decrease in CGRP was 18% and 27%, respectively. The tissue concentrations of SP and CGRP in ipsilateral ankle joints and dorsal root ganglia were consistently correlated in normal as well as arthritic rats. The present study shows that an interruption of the nerve supply to joints cannot fully prevent the development of arthritis, although it significantly reduces the occurrence of sensory neuropeptides.
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PMID:Effects of surgical denervation on substance P and calcitonin gene-related peptide in adjuvant arthritis. 747 86

Bilateral changes in the spinal cord and dorsal root ganglion content of the sensory peptides substance P and calcitonin gene-related peptide have been previously reported in animal models of arthritis which affect many joints within the body. The central nervous system has been implicated in the symmetry of joint involvement in human rheumatoid arthritis. We aimed to determine whether unilateral inflammation of the knee joint can also induce bilateral changes in the spinal cord. We have induced a monoarthritis in the knee joint of the rat and used quantitative immunocytochemistry to look at changes of these peptides in the dorsal horn of the spinal cord and the dorsal root ganglia. Furthermore we have examined the responses during the acute (three days) and the chronic (21 days) phases of the model. The data show that in the acute phase of the monoarthritis there is both an ipsilateral and contralateral response which increases the immunoreactive substance P and calcitonin gene-related peptide in the L4 level of the dorsal horn of the spinal cord. In the chronic phase of the monoarthritis, the contralateral side of the dorsal horn returned to control values whilst the ipsilateral side showed reduced amounts of immunoreactive substance P and calcitonin gene-related peptide compared to controls. We propose that the acute response, at three days, to unilateral inflammation is appropriate and has evolved to protect an organism against the original insult ipsilaterally, and the possibility of subsequent insult contralaterally.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoarthritis in the rat knee induces bilateral and time-dependent changes in substance P and calcitonin gene-related peptide immunoreactivity in the spinal cord. 750 83

An experimental arthritis induced by injection of kaolin and carrageenan into the knee joint resulted in a temporal relationship between glutamate dorsal horn content and paw withdrawal latency (PWL) which was positively correlated. Limping, guarding, increased response to heat stimuli (hyperalgesia) and altered staining patterns for glutamate (GLU), substance P (SP), and calcitonin gene-related peptide (CGRP) were monitored in the awake behaving arthritic rat over a 1 week time course. A decrease in PWL occurred on the side ipsilateral to the inflamed knee as early as 4 h after the induction of arthritis indicating the animals are hyperalgesic. The PWL remained decreased through the first 24 h. Computer-assisted quantification of the density of immunohistochemical staining indicated the content of GLU, SP and CGRP was altered differentially throughout the time course of the arthritis. The changes observed for all three substances occurred across the entire superficial dorsal horn. There was an initial depletion of SP followed by an increase in both SP and CGRP content which was maintained through 1 week. The GLU content was increased during the hyperalgesic period. The GLU changes followed the same time course and were positively correlated with the changes in PWL. In a small group of animals injected with kaolin and carrageenan, hyperalgesia did not develop. In this group of animals, no change in dorsal horn GLU or SP content occurred. Rather, there was an increase in CGRP content in the middle portion of the superficial dorsal horn which is the termination site of knee joint afferents. These data indicate that the development of heat hyperalgesia is dependent on GLU and possibly SP. Since inflammation of the knee joint does not involve the foot pad, the heat hyperalgesia observed during the first 24 h following induction of arthritis represents a central neuronal sensitization.
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PMID:Behavioral and immunohistochemical changes in an experimental arthritis model in rats. 751 59

In the mouse, arthritis was induced by a single sub-patellar intraarticular injection of bacterial collagenase. This procedure induces also patellar malalignment. A rich innervation of thin varicose calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactive fibers was found in the joint capsule, in the periosteum of the patella, in the synovial tissues at the lateral border of the patella, in the femoral groove, and in the subchondral bone of the patella and femur. Moreover, fibers were found in plica tissues between the quadriceps and patellar tendon, and the femoral groove. After the collagenase treatment, the general innervation pattern was comparable to that of the controls, but CGRP and SP innervation was no longer detectable with the antibodies in the plica tissues, and was to a lesser extent detectable in the fat pad of the patella, in the lateral borders of the patella and in the proliferated synovial tissues. Signs of degenerated axonal profiles were observed in these locations with a polyclonal antibody to the growth-associated protein GAP-43/B-50. At all the other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal.
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PMID:Innervation of the patella. An immunohistochemical study in mice. 751 3

The dorsal horn of the spinal cord, which forms the locus of first synapses in pain pathways, is an important site of interaction between calcitonin gene-related peptide (CGRP), substance P and enkephalin--the neuropeptides considered to be especially involved in the regulation of pain perception. Since adjuvant-induced arthritic rats provide a suitable model for peripheral inflammation and hyperalgesia, the possible alterations of immunoreactive CGRP, substance P and enkephalin as well as the binding sites for [125I]hCGRP alpha, [125I]substance P/neurokinin-1, (NK1) and [125I]FK-33-824/mu-opioid receptors were studied in the dorsal horn of the spinal cord receiving projections from the inflamed limbs. In arthritic rats compared to control animals, a bilateral increase in CGRP- and substance P-immunoreactive fibres and the presence of enkephalin-immunoreactive cell bodies were noted in the dorsal horn of the spinal cord. As for receptors, while a significant decrease in [125I]hCGRP alpha and [125I]substance P/NK1 binding sites was observed in selective layers, no measurable alteration in [125I]FK-33-824/mu-opioid binding sites was noted in any regions of the arthritic rat dorsal horn compared to the unaffected control rats. Following unilateral section of the peripheral nerve prior to induction of arthritis, CGRP- and substance P-immunoreactive fibres were markedly depleted and no enkephalin-positive neurons were observed in the ipsilateral dorsal horn. Analysis of receptor binding sites in denervated arthritic rats, however, exhibited differential responses, i.e. a significant increase in [125I]hCGRP alpha, a marked decrease in [125I]FK-33-824/mu-opioid and apparently no alteration in [125I]substance P/NK1 receptor binding sites were observed in the ipsilateral dorsal horn compared to the intact contralateral side. These results taken together provide anatomical evidence for a concerted role of these peptides in the regulation of adjuvant-induced hyperalgesia accompanying peripheral inflammation.
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PMID:Altered calcitonin gene-related peptide, substance P and enkephalin immunoreactivities and receptor binding sites in the dorsal spinal cord of the polyarthritic rat. 751 79

The effects of capsaicin on the sensory neuropeptides substance P and calcitonin gene-related peptide were analyzed in the ankle joints and dorsal root ganglia (L2-L6) of adult female Lewis rats. The study included 23 normal rats and 23 arthritic rats, all injected subcutaneously with capsaicin (total dose 200 mg/kg bw). Another two groups of animals from a previous study, i.e., 23 normal rats and 23 arthritic rats not given capsaicin served as controls. Adjuvant arthritis was induced by inoculation with heat-killed mycobacteria. The morphological distribution of sensory neuropeptides was assessed by immunohistochemistry and the tissue concentrations were determined by radioimmunoassay. In normal rats, capsaicin significantly reduced the concentrations of substance P and calcitonin gene-related peptide in ankle joints (54 and 36%, respectively) as well as dorsal root ganglia (40 and 54%, respectively). In arthritic rats those pretreated with capsaicin had significantly lower concentrations of substance P and calcitonin gene-related peptide in dorsal root ganglia (19 and 42%, respectively) compared to the arthritic controls. In the ankle joints, however, only the SP concentration was reduced (42%). Notably, this was accompanied by a 40% reduction in inflammatory response as assessed by comparing the ankle joint weights of the experimental groups. In general, there was a good correlation between the neuropeptide concentrations in ipsilateral ankle joints and the corresponding dorsal root ganglia as assessed in individual rats. The present study of adjuvant induced arthritis shows that capsaicin administration reduces the otherwise up-regulated levels of sensory neuropeptides in dorsal root ganglia and ankle joints. However, capsaicin at the dose given can only mitigate, not completely prevent the development of joint inflammation. Nonetheless, the findings suggest that antineuronal therapy targeted against specific neurotransmitters may prove useful in inflammatory joint disease.
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PMID:Capsaicin effects on substance P and CGRP in rat adjuvant arthritis. 753 50


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