Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031117 (peripheral neuropathy)
 10,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The density and distribution of reactivity for two lectins (soybean agglutinin (SBA) and RL-29), growth associated protein-43 (GAP-43) and the neuropeptides substance P and calcitonin gene-related peptide were analyzed in the spinal cord dorsal horn of rats with an experimental peripheral neuropathy. Twenty-eight days postsurgery, the density of label for RL-29 and GAP-43 was increased in laminae I and II on the experimental compared to the control side. In contrast, the density of neuropeptide label was decreased in the same region. Furthermore, on the experimental side, the distribution of both SBA and RL-29 reactivity was increased, extending into lamina III. We hypothesize that the increases in density and distribution of reactivity for the lectins and GAP-43, as well as the decreases in neuropeptide reactivity, reflect injury-induced regenerative changes in primary afferent terminals.
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PMID:Changes in lectin, GAP-43 and neuropeptide staining in the rat superficial dorsal horn following experimental peripheral neuropathy. 172 99

A 48-year-old man developed a marked and persistent hypercalcemia 3 months after admission for paraplegia resulting from severe peripheral neuropathy most likely of alcoholic etiology. Serum ionized calcium was elevated, and parathyroid hormone levels were low normal by the two separate radioimmunoassays. Urinary calcium excretion was markedly elevated, and serum 1,25-dihydroxyvitamin D level was decreased. An extensive clinical evaluation for possible occult malignancy, myeloma, and sarcoidosis as a cause of hypercalcemia produced no positive findings. Treatment with calcitonin caused prompt normalization of serum calcium, and its discontinuation resulted in recurrence of hypercalcemia. With improvement of neuropathy, the patient started active physical therapy. We gradually discontinued calcitonin, and the patient's serum calcium remained normal during the following 11 months. We discuss difficulties in both clinical and laboratory diagnosis of hypercalcemia of immobilization in the adult patient because no specific laboratory test is available.
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PMID:Hypercalcemia of immobilization in an adult patient with peripheral neuropathy. 253 19

An animal model of peripheral neuropathy resulting in a unilateral hyperalgesia has recently been developed. The N-methyl-D-aspartate (NMDA) antagonist MK-801 reduces the thermal hyperalgesia observed in this model. The goal of the present study was to determine whether the immunohistochemical changes in dorsal horn peptides shown by neuropathic animals could also be modified by MK-801. Changes in immunostaining densities of substance P (SP) and calcitonin gene-related peptide (CGRP) within the spinal cord of untreated (reference population) neuropathic rats and that of neuropathic rats treated for 7 days with MK-801 were quantified and compared. The reference neuropathic animals demonstrated thermal hyperalgesia and an ipsilateral decrease in SP staining density without an accompanying change in CGRP staining density. MK-801-treated animals showed a dose-dependent attenuation of the thermal hyperalgesia. The expected ipsilateral decrease in SP was prevented in neuropathic animals treated with a low dose (0.5 mg/kg) of MK-801, while a higher dose of MK-801 (1 mg/kg) resulted in an increase in SP staining ipsilateral to the injury. MK-801 treatment in naive rats caused a global increase in both SP and CGRP staining in the dorsal horn. However, this global increase failed to mask the changes in staining density in neuropathic animals following MK-801 treatment. The results suggest a functional interaction between excitatory amino acids (EAAs) and SP, with activation of NMDA receptors mediating depletion of SP in neuropathic animals. It is suggested that SP-containing interneurons are a target of the EAAs in the dorsal horn.
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PMID:Quantitative analysis of substance P and calcitonin gene-related peptide immunohistochemical staining in the dorsal horn of neuropathic MK-801-treated rats. 768 39

Alteration in the motoneurone contents of heat shock protein (hsp 70) and ubiquitin were studied in rats which had been subject to loose ligation of one common sciatic nerve. This results in a unilateral peripheral neuropathy which peaks at 14 days following ligation and is characterized by transient degeneration of both myelinated and unmyelinated nerve fibres, abnormal motor behaviours (posture of the hind limb, walking patterns) and thermal and mechanical allodynia of the hind paw. Hsp 70 and ubiquitin are proteins involved in protein metabolism and their expression is regulated during cellular stress. The contralateral unlesioned side was used as control. Motoneurone staining for hsp 70 and ubiquitin were differentially altered at the peak of the neuropathy. Axon damage resulted in a decrease in hsp 70 labeling while ubiquitin staining increased. At the same time motoneurones undergoing axon damage overstained for the immediate early gene encoded protein c-JUN and for nerve growth factor receptor (rNGF). In contrast, no clear alteration was seen, at that time, in the intensity of labeling for calcitonin gene-related peptide (CGRP). This study demonstrates that peripheral neuropathy resulting from loose ligation of the common sciatic nerve not only produces sensory alterations as previously reported but also leads to pronounced alterations in motoneurone functioning that could partly explain the observed abnormal motor behaviours. Results are discussed in accordance with presumed roles for hsp 70 and ubiquitin in protein metabolism and in relationship with possible interaction with c-JUN and rNGF expressions.
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PMID:Opposite effects of axon damage on heat shock proteins (hsp 70) and ubiquitin contents in motor neurons of neuropathic rats. 768 8

Glutamate is a major neurotransmitter of fine afferent fibers to the spinal cord. Neuropeptides are also released by the same fibers. We explored, by quantitative immunocytochemistry, the effects of two experimental manipulations of peripheral nerves on the levels of these two classes of mediators. Glutamate levels in the superficial dorsal horn of rats increased after chronic loose ligature of the sciatic nerve, a model for hyperpathic peripheral neuropathy. A similar increase was observed acutely, after stimulation of C fibers, but not A fibers, in the sciatic nerve. In contrast, immunostaining for substance P and calcitonin gene-related peptide decreased in the same region with both manipulations. The decrease in immunocytochemical levels of peptides is in agreement with previous observations and can result from activity-related depletion. We propose that the increase in glutamate levels reflects differences in the regulation and kinetics of amino acid versus peptide neuromediators.
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PMID:Glutamate immunocytochemistry in the dorsal horn after injury or stimulation of the sciatic nerve of rats. 809 61

Significant osteoporosis determined by skeleton radiography and bone densitometry was found in 15 patients with cerebrotendinous xanthomatosis (CTX) whose mean age was 31 +/- 11 years. In three CTX patients, bone biopsies confirmed osteoporosis. Nine patients also sustained bone fractures following minimal trauma. Serum 25-hydroxyvitamin D ([25-OHD] 14.6 +/- 6.6 ng/mL v [normal] 30.4 +/- 8.0 ng/mL; P < .001) and 24,25-dihydroxyvitamin D ([24,25(OH)2D] 1.2 +/- 0.4 ng/mL v [normal] 2.7 +/- 0.8 ng/mL; P < .001) levels were low. Serum concentrations of 1,25(OH)2D, calcium, inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and calcitonin were normal. Patients showed classic manifestations of CTX, including dementia, pyramidal and cerebellar insufficiency, peripheral neuropathy, cataracts, and tendon xanthomas associated with elevated serum cholestanol concentrations. These results demonstrate that extensive osteoporosis and increased risk of bone fractures are components of this inherited disease.
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PMID:Osteoporosis and increased bone fractures in cerebrotendinous xanthomatosis. 823 48

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

The chronic constriction injury (CCI) is an animal model of an experimental peripheral neuropathy. In this model, a mononeuropathy is produced by loosely ligating the left sciatic nerve of the rat with chromic gut suture (Bennett and Xie 1988). Maves et al. (1993) have proposed that chemical constituents of chromic gut suture influence the behavioral changes of rats with the CCI. Considering their results, we became interested in evaluating whether the type of suture material used to produce the CCI also affected spinal levels of calcitonin-gene-related peptide immunoreactivity (CGRP-ir) and substance P immunoreactivity (SP-ir), peptides that are associated with small primary afferent neurons. Using methods of radioimmunoassay (RIA), we measured levels of CGRP-ir and SP-ir in the dorsal quadrants of approximately the lumbar 4-5 (L4-L5) spinal segments of rats with a CCI induced using polyglactin (Vicryl), plain gut, or chromic gut suture. We observed bilateral decreases in CGRP-ir and SP-ir 60 days after a CCI induced with chromic gut suture, but no changes in peptide levels after a CCI induced with either polyglactin or plain gut suture. These results suggest two possibilities: (1) chromic gut suture, when used to produce the CCI, has more than just a constrictive effect on the sciatic nerve, and/or (2) different suture materials produce changes in CGRP-ir and SP-ir with a differential time-course. Our experiments are unable to distinguish between these two possibilities.
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PMID:Chromic gut suture reduces calcitonin-gene-related peptide and substance P levels in the spinal cord following chronic constriction injury in the rat. 878 15

The time course of histochemical changes in the dorsal horn of rats subjected to an experimental peripheral neuropathy has been examined. Qualitative and quantitative analyses of the changes in dorsal horn staining were made for soybean agglutinin (SBA)-binding glycoconjugates, the soluble lectins RL-14.5 and RL-29, the growth-associated protein (GAP)-43, and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). These analyses were made at various time points after chronic constriction of the sciatic nerve. Quantitative analysis indicated that staining density increased in the normal territories stained for SBA-binding glycoconjugates, RL-14.5, RL-29, and GAP-43 on the neuropathic side compared with the control side. In addition, there was an extension of the territories stained for SBA-binding glycoconjugates and RL-29 ipsilateral to the injury. The peak increases occurred at 14 or 28 days, followed by a decrease toward control levels by 70 days. In contrast, the staining density for SP in the ipsilateral dorsal horn decreased at 3 and 5 days and reached a peak decrease at 14 days. Then, the staining for SP returned toward control values. The staining for CGRP was unchanged at all time points examined. Dorsal rhizotomies ipsilateral to the nerve injury in neuropathic rats indicated that the increases in staining were attributable to changes in primary afferent neurons. These data suggest that peripheral neuropathy causes complex degenerative and regenerative changes in the central branches of primary afferent neurons. The associated synaptic reorganization may contribute to the sensory abnormalities that accompany peripheral neuropathy.
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PMID:Time course of degenerative and regenerative changes in the dorsal horn in a rat model of peripheral neuropathy. 906 34

Understanding pain or, more precisely, the different types of pain, is above all a question of understanding its physiological mechanisms and, in this regard, the role of basic research has without doubt been to trigger the development of new therapeutic strategies. In an approach to these problems, the main international teams involved in pain research have attempted to develop models of experimental pain in rats. Clearly, research aimed at developing these models is controlled by certain ethical considerations; however, in this context, the end must surely justify the means. The main models used (acute or chronic inflammation, rheumatoid arthritis, peripheral neuropathy) certainly do not give a comprehensive representation of all the pain syndromes encountered in clinical practice, but they do provide new data concerning the physiological, behavioural and pharmacological aspects of pain. While giving a brief description of the complexity of the pain circuit, this article also makes reference to certain pharmacological approaches to the treatment of pain. Peripheral nociceptive messages are conveyed by a mosaic of unmyelinated free fibres distributed throughout cutaneous, muscular and articular tissue, and within the visceral walls. They are then transmitted via various nerve endings (polymodal nociceptors) by small diameter A delta and C fibres, which are activated by mechanical, thermal and chemical stimuli. It is nevertheless difficult to ascertain whether these small diameter fibres are involved only in nociception (specific nociceptors) or whether pain causes an excessive activation of these receptors, which under normal conditions have a role in the reflex that regulates various functions (nonspecific nociceptors). Numerous chemical substances play a part in generating nociceptive impulses (e.g. histamine, serotonin, prostaglandins). Furthermore, the role of neuropeptides, such as calcitonin gene-related peptide and particularly substance P, has been clearly demonstrated in the activation of early neurogenic inflammation. Other substances, such as bradykinin and cytokines, are involved in prolonging the sensation of pain. Nerve growth factor also prolongs the sensation of pain by increasing the cellular excitability of nociceptors and promoting the action of the sympathetic nervous system, which has a major role in controlling pain. The very great diversity of all these interacting substances makes the pharmacological treatment of pain extremely complex. Nevertheless, new therapeutic advances are providing interesting approaches, particularly the development of specific inhibitors of cyclo-oxygenase 2 (COX 2), which is produced by the inflammatory process. Such inhibitors would preserve COX 1, which is both constitutive and physiological, and thereby provide improved tolerability compared with currently used NSAIDs, which act upon both COX pathways. A major focus of research relating to new analgesics is the development of synthetic antagonists of bradykinin, substance P and N-methyl-D-aspartate receptors. An improved understanding of anatomical and electrophysiological processes has led to the discovery of new ascending pathways that transmit nociceptive messages to the reticular formation, the hypothalamus, and the amygdala, as well as to certain areas of the cortex. As a result the notion of one single pain centre is no longer valid. This idea is further reinforced by the knowledge that, at different stages of the pain pathway, different control systems constantly modulate the transmission of nociceptive information. Consequently, at a spinal level, activation of the large diameter cutaneous fibres (A alpha et beta) blocks pain stimuli transmitted by the small diameter fibres. Knowledge of this "gate control' mechanism of the posterior horn of the spinal cord is put to practical application in treatments involving transcutaneous electrical nerve stimulation. (ABSTRACT TRUNCATED)
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PMID:[The complexity of physiopharmacologic aspects of pain]. 919 Mar 19


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