Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain following nerve injury is thought to involve central nervous system Ca(2+)-mediated neuronal plastic changes. This study provides evidence that induction and/or maintenance of post-injury neuropathic pain behaviors in the rat is associated with increases in membrane-bound protein kinase C (PKC), a Ca(2+)-dependent process known to mediate central nervous system neuronal plasticity. In addition, spinal cord administration of GM1 ganglioside, an intracellular inhibitor of PKC translocation/activation, reverses both increased levels of membrane-bound PKC and pain-related behaviors. Thus, persistent post-injury neuropathic pain may be mediated by the initiation of excitatory neuropathological processes resulting from an increase in membrane-bound PKC.
 ...
PMID:Pain-related increases in spinal cord membrane-bound protein kinase C following peripheral nerve injury. 139 64

Injured sensory axons with endings trapped in a nerve-end neuroma become a source of abnormal impulse discharge and neuropathic pain. We have examined the ultrastructure of such endings anterogradely transported WGA-HRP and freeze-fracture replication, with emphasis on the postinjury period during which the abnormal neural discharge is maximal. Most axons ended in a terminal swelling, depleted of myelin but surrounded by Schwann cell processes. These 'neuroma endbulbs' were richly packed with membrane-bound organelles, and had a smoothly undulating surface with (in neuromas of several weeks standing) a moderate number of short filopodia. Massive sprouting did not occur until several months postinjury. Both p- and e-faces of endbulb axolemma had larger intramembranous particles, on average, than corresponding internodal membrane of control axons. This change, interpreted as indicating remodelling of axolemmal channel (and perhaps receptor) content, may be related to the abnormal electrical behavior of neuroma afferents.
 ...
PMID:Ultrastructure of afferent axon endings in a neuroma. 171 40

A new case of Tangier disease is described. It is the 33rd case in world literature and only the 2nd in Italy. A 52-year-old man showed a widely spread neuropathy with facial diplegia, bilateral wasting of hand muscles and dissociated loss of pain and temperature sensation sparing the distal parts of the lower limbs. Clinical and laboratory data were typical of Tangier disease. A histological and ultrastructural study of the patient's superficial peroneal nerve and brevis peroneus muscle was carried out. A revision of the clinical and neuropathological aspects of the neuropathy of Tangier disease allowed our case to be included within a particular neurological description. Four patients with similar clinical characteristics had been noted previously. Clinical, morphological and biochemical data suggest the hypothesis that there are two different neuropathic forms of Tangier disease.
 ...
PMID:Neuropathy in Tangier disease: A clinicopathologic study and a review of the literature. 408 16

This report describes a third mucopolysaccharidosis in animals: canine mucopolysaccharidosis VII. The affected dog was the offspring of a father-daughter mating. Weakness in the rear legs was evident at 8 weeks of age and became progressively worse. He had a large head, a shortened maxilla, and corneal granularities. Most joints were extremely lax, easily subluxated, with joint capsules that were swollen and fluctuant. The dog was alert and had apparently normal pain perception. At 13 months of age, there was radiographic evidence of extensive skeletal disease including bilateral femoral head luxation, abnormalities in the shape and density of the carpal and tarsal bones, radiolucent lesions of the epiphyseal regions of most long bones, and cervical vertebral dysplasia and platyspondylia. The electrophoretic pattern of precipitated glycosaminoglycans indicated a predominance of chondroitin sulfate. The animal died suddenly from gastric dilatation. There was generalized hepatomegaly, thickening of the atrioventricular heart valves, and generalized polyarthropathy. Vacuolated cytoplasm was observed in hepatocytes, keratocytes, fibroblasts, chondrocytes and cells of the synovial membrane, retinal pigment epithelium, and cardiac valves. Neurons had cytoplasmic vacuoles. Electron microscopy demonstrated membrane-bound cytoplasmic inclusions in polymorphonuclear leukocytes, hepatocytes, synovium, heart valves and spleen. The activities of 12 lysosomal hydrolases were determined in liver from the affected and control dogs: beta-glucuronidase (EC 3.2.1.31), beta-hexosaminidases A and B (EC 3.2.1.30), alpha-hexosaminidase (EC 3.2.1.-), alpha-L-iduronidase (EC 3.2.1.76), alpha-galactosidase A (EC 3.2.1.22), beta-galactosidase (EC 3.2.1.23), arylsulfatases A and B (EC 3.1.6.1), acid alpha-mannosidase (EC 3.2.1.24), acid beta-mannosidase (EC 3.2.1.25), and N-acetyl-D-galactosamine-6-sulfate sulfatase (EC 3.1.6.-).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Beta-glucuronidase deficiency in a dog: a model of human mucopolysaccharidosis VII. 643 80

Emotional-pain stress leads to accumulation of lipid peroxidation products in rat brain tissues and to an increase in the number of antibrain antibodies against water-soluble and membrane-bound antigens in rat blood. An injection of the free radical scavenger, 4-methyl-2.6-di-tert-butylphenol to experimental animals eliminates the accumulation of lipid peroxidation products "in vivo" and completely prevents the appearance of antibrain antibodies. The activation of lipid peroxidation under stress may be regarded as a possible cause of the brain-specific antibodies release into the blood flow.
 ...
PMID:Activation of lipid peroxidation: a mechanism triggering the autoimmune response. 668 40

Cluster headache remains a disease with almost totally unknown etiology and poorly understood pathogenesis. Some evidence has been presented to suggest that histamine released from mast cells might possibly be responsible for the initiation of pain attack. The authors present ultrastructural data concerning cutaneous mast cells in the painful region in patients suffering from cluster headache. The biopsies were taken between attacks in a bout. The fine structure of the mast cells (namely swollen granules, zones of decreased density, membrane-bound vesicles and granular fusion) are consistent with the dissolution pattern of secretion. The possible role of antidromic-reflex activation of the mast cells is also discussed.
 ...
PMID:Mast cells in cluster headache. Ultrastructure, release pattern and possible pathogenetic significance. 673 78

The development of tolerance to the analgesic effects of morphine as well as morphine dependence were greatly reduced by co-administration with morphine of GM1 ganglioside, a substance reported to block the translocation of protein kinase C (PKC) from cytosol to membrane of neurons. Rats made tolerant to intrathecal administration of morphine showed increased membrane-bound PKC in the superficial layers (laminae I and II) of the spinal cord dorsal horn but not in deeper layers. This increase was prevented by co-administration with morphine of GM1 ganglioside. These results indicate that the translocation and activation of PKC may be a critical step in the development of opiate tolerance and dependence. Modulation of PKC translocation and activation may prove useful for the management of pain and opiate addiction.
Pain 1995 Jun
PMID:The development of morphine tolerance and dependence is associated with translocation of protein kinase C. 889 58

The cases of three patients with primary carcinoid tumor of the testis were reported. The patients were 41, 44, and 83 years of age. At initial examination, all three had testicular masses with or without associated pain, and none had the carcinoid syndrome. The tumors measured 4.3 cm, 3.0 cm, and 6.5 cm in dimension. All three tumors manifested classic histologic features of carcinoid tumors. The neoplastic cells exhibited argyrophilia, and all were immunoreactive to chromogranin, serotonin, neuron-specific enolase, and cytokeratin. Two tumors had positive test results for gastrin and one had positive test results for substance P and vasoactive intestinal polypeptide. No tumors reacted with somatostatin, insulin, pancreatic polypeptide, or placental alkaline phosphatase. Intracytoplasmic, membrane-bound, round-to-elliptical pleomorphic granules were identified by ultrastructural analysis in all cases. DNA flow cytometric analysis revealed a low degree (near-diploid) DNA aneuploidy in all cases, with a DNA index of 1.15 in two tumors and 1.3 in the third tumor. The three patients are alive and well 11 years, 7 years, and 6 months, respectively, after diagnosis. A total of 57 cases of this entity, including the 3 reported here, have been reported. Of these, 43 were pure carcinoid, and 14 were associated with teratoma; 6 (11.6%) patients developed metastases. Tumor size and the presence of carcinoid syndrome have been found to correlate with metastatic potential. Neither tumor necrosis nor local tumor invasion (into vessels, tunica albuginea, etc.) correlated with adverse prognosis. Carcinoid tumor of the testis is a rare indolent neoplasm with potential for distant metastases.
 ...
PMID:Primary carcinoid tumor of testis. Immunohistochemical, ultrastructural, and DNA flow cytometric study of three cases with a review of the literature. 768 60

Opioid drugs exert a wide spectrum of physiological and behavioral effects, including effects on pain perception, mood, motor control and autonomic functions. The effects of opioids are mediated via a family of membrane-bound receptors, of which the most extensively characterized are the mu, delta and kappa receptors. We have now cloned the human homolog of the mu opioid receptor and, in the present study, we have examined its pharmacological profile. The human mu receptor has high affinities for several alkaloids of high abuse potential as well as a variety of peptide and nonpeptide drugs characterized previously as mu-selective, but not delta- or kappa-selective. Most importantly, the human mu receptor has higher affinity for morphine and methadone than does the rat mu receptor, despite the fact that these receptors are 95% identical at the amino acid level. The labeling of the receptor by agonist was decreased by nonhydrolyzable GTP analogs and by pertussis toxin treatment of cells expressing the human mu receptor, consistent with the coupling of the receptor to guanine nucleotide binding proteins. The human mu receptor functionally couples to the inhibition of adenylyl cyclase in a stereospecific and naloxone-reversible manner. We have also investigated the distribution of mRNAs encoding the mu receptor in human brain by Northern analysis, which demonstrates the existence of multiple transcripts of 13.5, 11, 4.3 and 2.8 kb, which were highly expressed in the hypothalamus, thalamus and subthalamic nucleus, more moderately expressed in the amygdala and caudate nucleus and which demonstrated lowest levels of expression in the hippocampus, substantia nigra and corpus callosum.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Characterization of the cloned human mu opioid receptor. 781 59

Opioid drugs, such as morphine, and the endogenous opioid peptides, namely the enkephalins, endorphins, and dynorphins, exert a wide spectrum of physiological and behavioral effects, including effects on pain perception, mood, motor control, and autonomic functions. These effects are mediated via membrane-bound receptors, of which the best characterized are the kappa, delta, and mu receptors. The existence of these distinct types of opioid receptors has recently been confirmed by molecular cloning. In the present study, we have examined the pharmacological profiles of the cloned kappa, delta, and mu receptors using a battery of widely employed opioid agents. Our results suggest that the cloned kappa and mu receptors have pharmacological characteristics similar to those of the endogenously expressed kappa 1 and mu receptors, respectively. The cloned delta receptor displays a pharmacological profile consistent with that of a delta 2 receptor. Opioid agents with abuse potential possess high affinities for the mu receptor. The availability of the cloned receptors will facilitate the identification and development of more specific and selective compounds with greater therapeutic potential and fewer undesirable side effects.
 ...
PMID:Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. 811 80


1 2 3 4 5 6 7 8 9 10 Next >>