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

This paper describes a study on a dynorphin converting enzyme in spinal cord homogenates from rats with experimental arthritis after adjuvant injection into one hindpaw. The enzyme resembles a neutral cysteine endopeptidase which cleaves the opioid peptide dynorphin B and generates its N-terminal fragment, Leu-enkephalin-Arg6 with opioid activity. It exhibits considerably lower activity against dynorphin A and alpha-neoendorphin, the two other prodynorphin derived peptides. The enzyme showed significantly higher activity in the dorsal part than in the ventral part of the spinal cord. A significant decrease in enzyme activity was observed in the dorsal spinal cord during inflammation as compared to vehicle-injected controls. This decrease paralleled a decrease in the tissue level of Leu-enkephalin-Arg6. These data thus indicate that adjuvant-induced arthritis may generate an important change in a converting enzyme acting on peptide structures, which may be involved in pain modulation. Therefore, a functional role of the present enzyme in the regulation of pain-related peptides is suggested.
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PMID:Dynorphin converting enzyme in the rat spinal cord. Decreased activities during acute phase of adjuvant induced arthritis. 154 65

Noxious stimulation in vivo provokes the transcriptional activation of several genes which are thought to play an important role in the phenomena of stress and pain. In the rat, the expression of the c-fos proto-oncogene is rapidly induced upon noxious stimulation in defined neurons in the dorsal horn of the spinal cord. Interestingly, expression of the prodynorphin gene, which is thought to be involved in the endogenous mechanisms for pain/stress control, also localizes in the same anatomical area. Fos proteins are known to associate in transcriptional complexes with the products of the jun family constituting nuclear factor AP-1. These considerations prompted us to analyse the expression of the jun gene family members c-jun, jun B and jun D in rats subjected to noxious stimulation. We present data indicating that in unstimulated animals the transcripts of the three genes are differentially expressed and abundant within the various laminas of the lumbar spinal cord. Surprisingly, upon stimulation only the jun B transcript is augmented, being co-localized with Fos in a subset of neurons of the medial dorsal horn.
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PMID:Co-induction of jun B and c-fos in a subset of neurons in the spinal cord. 190 Mar 56

Noxious stimulation provokes the activation of genes that are thought to play a crucial role in the phenomena of stress and pain. Among these is the prodynorphin gene. By double-labeling in situ hybridization/immunohistochemistry, we show that increased prodynorphin gene expression is preceded, in the same neurons, by an early induction of c-fos. Inspection of the prodynorphin promoter region revealed the presence of several AP-1-like sequences. We demonstrate that only one of these sites is a functional AP-1 element. It is constituted by the noncanonical TGACAAACA sequence, in which the palindromic structure is partly conserved by the 3' terminal CA dinucleotide. Transfection experiments in NCB20 neuroblastoma cells indicated that this site is a target of Fos/Jun trans-activation. Our results suggest that Fos/Jun oncoproteins may function as third messengers in the signal transduction mechanisms of stress/pain processes.
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PMID:Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene. 190 18

The influence of chronic arthritic pain upon the levels of mRNA encoding prodynorphin (mRNADYN) in the spinal cord of rats was evaluated by use of the RNA blot technique. Rats were rendered arthritic by inoculation of the tail-base with a suspension of Mycobacterium butyricum. Three weeks post inoculation, levels of mRNADYN revealed a pronounced alteration in arthritic rats by a factor of greater than or equal to 2.5 as compared to control animals. This rise was specific in that there was no change in total RNA content. These data indicate that the biosynthetic activity of the dynorphin system is facilitated under chronic pain. Together with our previous biochemical and behavioural data, a functional role of this system in the response to chronic pain is suggested.
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PMID:Prodynorphin gene expression is enhanced in the spinal cord of chronic arthritic rats. 243

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

The neuroanatomical distribution of dynorphin B-like immunoreactivity (DYN-B) was studied in the adult male and female albino rat. The distribution of DYN B in colchicine- and noncolchicine-treated animals was also compared to that of another opioid peptide derived from the prodynorphin precursor dynorphin A (1-8) (DYN 1-8), and an opioid peptide derived from the proenkephalin precursor met-enkephalin-arg-gly-leu (MERGL). DYN B cell bodies were present in nonpyramidal cells of neo- and allocortices, medium-sized cells of the caudate-putamen, nucleus accumbens, lateral part of the central nucleus of the amygdala, bed nucleus of the stria terminalis, preoptic area, and in sectors of nearly every hypothalamic nucleus and area, medial pretectal area, and nucleus of the optic tract, periaqueductal gray, raphe nuclei, cuneiform nucleus, sagulum, retrorubral nucleus, peripeduncular nucleus, lateral terminal nucleus, pedunculopontine nucleus, mesencephalic trigeminal nucleus, parabigeminal nucleus, dorsal nucleus of the lateral lemniscus, lateral superior olivary nucleus, superior paraolivary nucleus, medial superior olivary nucleus, ventral nucleus of the trapezoid body, lateral dorsal tegmental nucleus, accessory trigeminal nucleus, solitary nucleus, nucleus ambiguus, paratrigeminal nucleus, area postrema, lateral reticular nucleus, and ventrolateral region of the reticular formation. Fiber systems are present that conform to many of the known output systems of these nuclei, including major descending pathways (e.g., striatonigral, striatopallidal, reticulospinal, hypothalamospinal pathways), short projection systems (e.g., mossy fibers in hippocampus, hypothalamo-hypophyseal pathways), and local circuit pathways (e.g., in cortex, hypothalamus). The distribution of MERGL was, with a few notable exceptions, in the same nuclei as DYN B. From these neuroanatomical data, it appears that the dynorphin and enkephalin peptides are strategically located in brain regions that regulate extrapyramidal motor function, cardiovascular and water balance systems, eating, sensory processing, and pain perception.
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PMID:Distribution of dynorphin and enkephalin peptides in the rat brain. 287 59

Cerebrospinal fluid activity of a dynorphin-converting enzyme transforming prodynorphin-derived peptides to [Leu]enkephalin-Arg6 was measured in 12 women at term pregnancy before cesarean section and in eight nonpregnant, nonpuerperal controls. In pregnant women, the dynorphin-converting enzyme activity was significantly lower (mean +/- SD 6.8 +/- 3.8 U/L) than in nonpregnant controls (11.7 +/- 2.6 U/L; P less than .01). Furthermore, prodynorphin-derived [Leu]enkephalin-Arg6-containing polypeptides were significantly increased in samples from pregnant women (P less than .05). This indicates that a reduced activity of opioid peptide-degrading enzymes might contribute to an increased resistance to pain at term pregnancy.
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PMID:Cerebrospinal fluid activity of dynorphin-converting enzyme at term pregnancy. 289 24

Opioid peptides derived from proenkephalin and prodynorphin are differentially distributed in the spinal cord. Proenkephalin peptides are preferentially located in the sacral portion of the cord while prodynorphin peptides are concentrated in the cervical spinal cord. Mu opioid receptor are highly concentrated in superficial layers of the dorsal horn in all the spinal cord. Delta opioid receptor are more diffusely distributed in the gray matter of the spinal cord. These sites are principally located in cervical and thoracic portions of the spinal cord. Kappa opioid receptors are highly concentrated in the superficial layers of the lumbo-sacral spinal cord. Its density decreased in the upper levels of the spinal cord. It appears that mu opioid receptors are indifferentially activated by thermal, pressure and visceral nociceptive inputs. Delta receptors are more likely to be involved in thermal nociception while kappa opioid binding sites are associated to visceral pain nociceptive inputs.
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PMID:Pain, nociception and spinal opioid receptors. 615 41

To determine whether opioid peptide-receptor pharmacological association found in vitro (e.g., enkephalin-delta, dynorphin-kappa) predict anatomical relationships in situ, immunocytochemical and receptor autoradiographic studies were carried out on adjacent sections from the same brains of formaldehyde-perfused rhesus monkeys. Apparent mu and kappa opioid receptors (labeled, respectively, by [3H] naloxone and [3H]bremazocine under different incubation conditions), but not delta opioid receptors (labeled by [3H]D-Ala2, D-Leu5-enkephalin), survived the fixation procedure, and were found to be colocalized throughout the brain. We have observed complex associations between these binding sites and one, two, or all three opioid peptide systems (i.e., proopiomelanocortin, proenkephalin, and prodynorphin) in different brain regions. These multiple opioid peptide-receptor subtype associations are apparent, for example, in neural systems involved in the processing of pain stimuli, and may be important for mediating different types of analgesia. Since differential processing of proenkephalin and prodynorphin can give rise to opioids of varying receptor selectivities, the colocalization of opioid receptor subtypes may signify that such processing is a key regulatory event in determining which receptor subtype is activated and, thus, the physiological consequences of opioid neurotransmission.
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PMID:Anatomical relationship between opioid peptides and receptors in rhesus monkey brain. 615 4

The opioid peptide system in the brain is probably the most extensive and diverse peptidergic transmission system. Three peptide precursors, pro-opiomelanocortin, proenkephalin and prodynorphin produce over 20 opioid peptides collectively known as the endorphins, enkephalins and dynorphins. Their effects are mediated by three receptors mu, delta and kappa, and the opioid system has control over several physiological functions including pain, locomotion, mood, diuresis, thermoregulation, stress, respiratory, gastrointestinal and cardiovascular function. Lead treatment (primarily using rat models) has shown that exposure to this metal in the perinatal period alters the development of endorphins and enkephalins, toxic effects which for the pro-opiomelanocortin products may be manifested at the gene level. Lead also alters the development of mu and delta receptors and biological responses to opioids such as analgesia, locomotion and stress responses. There are indications that the dynorphin/kappa opioid system is less affected than the mu and delta systems and this may suggest vulnerability to toxicity in the postnatal period as kappa systems are fully developed at birth whilst mu and delta systems are immature. In addition, hypothalamic and pituitary disruption of opioid peptides, plus alteration of stress-mediated activity by lead point to toxicity upon opioid controlled hormonal function. Comparative studies with other CNS neurochemicals and measures of blood lead levels suggest that opioid peptides are among the most sensitive neurotransmitter/neurohormonal systems to toxic insult by lead.
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PMID:Lead toxicity and alterations in opioid systems. 824 86


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