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)

Orphanin FQ (OFQ) is the recently isolated endogenous ligand for the orphan opioid-like receptor, LC132. Initial reports suggested that OFQ increased pain sensitivity when injected intracerebroventricularly (i.c.v.) in mice. However, we have recently demonstrated that OFQ is instead an anti-opioid peptide that reverses morphine- and opioid-mediated stress-induced antinociception. Morphine binds to multiple opioid receptor types (mu, delta, and kappa). The present study was designed to examine specific interactions of OFQ with antinociception mediated by each receptor type. To this end, mice were administered i.c.v. cocktails containing either vehicle or OFQ (10 nmol) and a mu-specific ([D-Ala2, N-Me-Phe4-Gly-ol]enkephalin; DAMGO; 0-0.1 nmol), delta-specific ([D-Pen2, D-Pen5]enkephalin; DPDPE; 0-50 nmol), or kappa-specific (U-50,488H; 0-1000 nmol) agonist. As we have shown previously, OFQ alone had no effect on nociceptive sensitivity. OFQ was, however, able to completely block supraspinal antinociception produced by all three receptor type-selective agonists. We conclude, therefore, that OFQ functionally antagonizes mu (and (opioid receptors, and may play a general role in opioid modulation.
 ...
PMID:Functional antagonism of mu-, delta- and kappa-opioid antinociception by orphanin FQ. 887 1

A heptadecapeptide (orphanin FQ or nociceptin) was recently identified as an endogenous ligand for the orphan opioid-like receptor. Here we report that intrathecal orphanin FQ produces dose-dependent depression of a spinal nociceptive flexor reflex in the rat. Furthermore, administration of orphanin FQ in rats with intrathecal catheters produced behavioural antinociception in the tail flick test with no signs of sedation or motor impairment. The reflex depressive effect of orphanin FQ was not reversed by antagonists of opioidergic, alpha 2-adrenergic and GABA-A receptors. Thus, orphanin FQ may suppress nociceptive input at the spinal level through an novel mechanism. Orphanin FQ or agonists of its receptor may represent novel analgesics for pain conditions which are not responsive to existing pharmacological therapy.
 ...
PMID:Nociceptin or antinociceptin: potent spinal antinociceptive effect of orphanin FQ/nociceptin in the rat. 893 Sep 65

Orphanin FQ (OFQ), the endogenous ligand for the orphan opioid receptor, LC132, was recently isolated and characterized. The anti-opioid role of OFQ in supraspinal pain modulation was demonstrated by our previous observations that intracerebroventricular (i.c.v.) OFQ administration dose-dependently reverses systemic morphine antinociception and opioid-mediated stress-induced antinociception. The present study was designed to evaluate whether OFQ also modulates the antinociceptive actions of morphine in the spinal cord. Immediately after assessment of baseline nociceptive sensitivity on the 49 degrees C tail-withdrawal assay, mice of both sexes were given i.c.v. or intrathecal (i.t.) cocktails of morphine (0, 1, 10 or 50 micrograms [0-135 nmol]) and OFQ (0 or 10 nmol), and re-tested 15, 30 and 60 min later. OFQ alone did not affect nociceptive sensitivity when administered by either route. Following i.c.v. administration, the antinociception produced by 10 micrograms morphine was completely reversed by 10 nmol OFQ; antinociception induced by 50 micrograms morphine was significantly antagonized. In contrast, OFQ was completely ineffective against antinociception induced by i.t. morphine. These findings indicate that the anti-opioid actions of OFQ are restricted to supraspinal central nervous system sites.
 ...
PMID:Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. 893 Sep 72

The endogenous opioid receptor-like1 (ORL1) ligand, nociceptin/orphanin FQ (FGGFTGARKSARKLANQ), a heptadecapeptide structurally resembling dynorphin A, has recently been identified. The wide distribution of ORL1 mRNA and nociceptin/orphanin FQ precursor in the CNS, particularly in the limbic system regions and in several areas known to be involved in pain perception, suggests that nociceptin/orphanin FQ is potentially endowed with various central functions. In general, activation and/or inactivation of regulatory peptides occur through the action of cell surface peptidases. The physiological mechanisms under which nociceptin/orphanin FQ is metabolized should lead to a better understanding of its physiological functions. Mouse brain cortical slices were incubated in medium containing the heptadecapeptide in the presence or in the absence of peptidase inhibitors. The critical sites of enzymatic cleavage are Phe1-Gly2, Ala7-Arg8, Ala11-Arg12, and Arg12-Lys13 bonds. The major role played by metallopeptidases was confirmed by the complete protection of metabolism in the presence of EDTA. Aminopeptidase N and endopeptidase 24.15 are the two main enzymes involved in nociceptin/orphanin FQ metabolism, whereas endopeptidase 24.11 (involved in enkephalin [YGGFM(L)] catabolism) does not appear critically involved in nociceptin/orphanin FQ metabolism. The physiological relevance of aminopeptidase N and endopeptidase 24.15 in the heptadecapeptide metabolism remains to be determined.
 ...
PMID:Nociceptin/orphanin FQ metabolism: role of aminopeptidase and endopeptidase 24.15. 897 46

We reported here purification and characterization of a novel heptadecapeptide in bovine brain as an endogenous ligand for ROR-C, an opioid receptor homologue cloned from rat cerebrum. The amino acid sequence of the peptide that we purified is identical to those recently identified as nociceptin in rat brain and orphanin FQ in porcine brain. The peptide inhibited the forskolin-induced cyclic AMP accumulation in ROR-C expressing Chinese hamster ovary cells. Studies on inhibitory activity of cyclic AMP accumulation and Northern blot analysis showed that the peptide and its precursor mRNA are present in a number of brain regions, less abundant in the spina cord, and negligible in the cerebellum. In situ hybridization analysis revealed that hybridization-positive neurons were distributed in the superficial layer (lamina I) of the dorsal horn and were also interspersed between the tract of Lissauer in the spinal cord. Intrathecal administration of the peptide into conscious mice induced allodynia, a pain response to innocuous tactile stimuli, in a beli-shaped manner. These results demonstrate that the peptide exists in the brain and spinal cord and plays an important role in pain transmission.
 ...
PMID:Identification and characterization of an endogenous ligand for opioid receptor homologue ROR-C: its involvement in allodynic response to innocuous stimulus. 903 23

The newly discovered peptide nociceptin/orphanin FQ has been found to increase reactivity to pain and to influence locomotor activity after intracerebroventricular administration. This study investigated the possible role of hippocampal nociceptin/orphanin FQ in spatial learning and in spontaneous locomotion. Male rats were trained in the Morris water task after microinjection of 10 nmol nociceptin/orphanin FQ or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal hippocampus. Nociceptin/orphanin FQ was found to severely impair spatial learning without interfering with swimming performance. Intrahippocampal injection of nociceptin/ orphanin FQ markedly decreased exploratory locomotor activity including vertical movements (rearing). The data suggest that nociceptin/orphanin FQ is a potent modulator of synaptic plasticity within the hippocampus.
 ...
PMID:Nociceptin/orphanin FQ microinjected into hippocampus impairs spatial learning in rats. 904 83

The influence of orphanin FQ (OFQ) (a newly discovered 17-amino acid peptide) on acupuncture analgesia (AA) was assessed in rat tail-flick model. Intracerebroventricular (i.c.v.) injection of OFQ (1 microgram) elicited a significant decrement of pain threshold which was abolished by the repeated pretreatment with antisense oligonucleotide (ASO) to OFQ receptor. Electroacupuncture (EA) induced an obvious analgesic effect; when OFQ was used combined with EA, it showed a dose-dependent effect on antagonizing the EA analgesia. When rat was repeatedly i.c.v. injected with ASO to block the synthesis of OFQ receptor, the EA analgesia was enhanced markedly. In this instance, the OFQ did not show antagonistic effect on EA analgesia any more. The results suggest that the OFQ play its antagonistic role on EA analgesia via activating OFQ receptor.
 ...
PMID:Antagonistic action of orphanin FQ on acupuncture analgesia in rat brain. 905 Nov 67

1. The present study was designed to investigate further the effects of the newly discovered orphanin FQ (OFQ)-the endogenous ligand for the orphan opioid receptor (called, e.g., ORL, and LC132)-on pain modulation in the rat. We used the tail-flick assay as a nociceptive index. 2. When injected into a cerebral ventricle, OFQ (4 fmol-10 nmol) has no effect on basal tail-flick latency by itself at any dose, but dose-dependently antagonizes systemic morphine analgesia (400 fmol 50 nmol). 3. Injected intrathecally, OFQ (3 and 10 nmol) displayed an analgesic effect without producing motor dysfunction, and potentiated morphine analgesia (1 and 10 nmol). 4. The anti-opioid effect of OFQ in rat brain and the high level of expression of LC132/ORL, receptor in the locus coeruleus indicated a possible role of OFQ in the precipitation of opiate withdrawal symptoms. However, no such precipitation was observed by OFQ in morphine-dependent rats.
 ...
PMID:Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat. 905 7

Recent studies suggest that the novel opioid peptide orphanin FQ (OFQ) is involved in pain modulation. We found that intracerebroventricular (i.c.v.) administration of OFQ in the rat produced a dose-dependent antagonism of the analgesia induced by 100 Hz electroacupuncture (EA) stimulation as measured in the radiant heat tail-flick assay. Antisense oligonucleotides injected i.c.v. potentiated EA analgesia, presumably by interfering with the expression of the OFQ receptor in brain. These results suggest that endogenous OFQ exerts a tonic antagonistic effect on EA-induced analgesia. No such antagonism was observed when OFQ was injected intrathecally (i.t.). Rather, it appears that spinal OFQ produced a marked analgesic effect and enhanced EA-induced analgesia. These findings are consistent with the experimental results obtained in rats where morphine-induced analgesia is antagonized by i.c.v. OFQ and potentiated by i.t. OFQ.
 ...
PMID:Involvement of endogenous orphanin FQ in electroacupuncture-induced analgesia. 908 Apr 36

Nociceptin (Orphanin FQ) is a newly discovered endogenous heptadecapeptide substrate for the opioid-receptor-like 1 receptor, a G protein coupled receptor that bears striking amino acid sequence homology to opiate receptors. In rats, intrathecal (i.t.) administration of nociceptin is without effect on basal thresholds for responsiveness to electric food shock. However, during either late gestation or its hormonal simulation, when nociceptive thresholds are elevated by approximately 70%, i.t. nociceptin substantially attenuates jump thresholds in a dose-dependent fashion. This hypoalgesic effect of nociceptin is not limited to attenuating the gestational or sex steroid-induced increment in pain thresholds. Following highest i.t. dose of nociceptin employed (20 nmol), the gestational or sex steroid-induced increment in jump thresholds is not only abolished but a significant hyperalgesia is observed. These results underscore the importance of the hormonal milieu to nociceptin hypoalgesic sensitivity. The potential contribution of spinal nociceptive pathways that utilize nociceptin to the etiology of extraordinary painful pregnancy and labor should not be ignored.
 ...
PMID:Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia. 909 28


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