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)

The nociceptin/orphanin FQ (N/OFQ) receptor (e.g. the human ortholog ORL1) has been shown to be pharmacologically distinct from classic opioid receptors. Recently, we have identified buprenorphine as a full ORL1 agonist using a reporter gene assay. For further functional analysis, buprenorphine's effects on ORL1 receptors were investigated using a K(+) channel (GIRK1) assay in Xenopus oocytes and GTPgammaS assay in CHO-K1 membrane preparations. In both assays, buprenorphine behaved as a partial agonist compared to nociceptin itself. The N/OFQ agonism of buprenorphine might contribute to actions of buprenorphine in pain models in vivo beside its mu- or kappa-opioid receptor mediated effects.
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PMID:Agonistic effects of the opioid buprenorphine on the nociceptin/OFQ receptor. 1099 49

Nociceptin (NC) and the opioid receptor like-1 receptors are widely distributed in areas of the neuraxis that are part of the descending modulatory pain system. We used the tail-flick assay in mice to assess the interaction between NC and other analgesic compounds acting on different areas of the descending pathway. Given by intracerebroventricular injection, NC induced hyperalgesia at 10 nmol (39% of reduction vs. control group). The same dose of NC reversed analgesia induced by distinct classes of analgesia-producing compounds such as morphine, dynorphin A or baclofen. NC caused a reduction of their antinociceptive effects: 61, 41 and 27%, respectively. Thus, NC at the supraspinal level appears to interact with both opioid and gamma-aminobutyric acid(B) systems producing anti-analgesic effects probably through the descending pathway for pain control.
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PMID:Nociceptin attenuates opioid and gamma-aminobutyric acid(B) receptor-mediated analgesia in the mouse tail-flick assay. 1099 54

The binding sites of nociceptin (also named orphanin FQ), the endogenous ligand of ORL1 (opiate receptor like 1), were localized in rat brain, using an autoradiographic procedure. High levels of binding were observed in the cingulate, retrosplenial, perirhinal, insular and occipital cortex, anterior and posteromedial cortical amygdaloid nuclei, basolateral amygdaloid nucleus, amygdaloid complex, posterior hippocampus, dorsal endopiriform, central medial thalamic, paraventricular, rhomboid thalamic, suprachiasmatic, ventromedial hypothalamic nuclei, mammillary complex, superficial gray layer of the superior colliculus, locus coeruleus, dorsal raphe nucleus. More moderate labelling was observed in the prefrontal, fronto-parietal, temporal, piriform cortex, dentate gyrus, anterior olfactory nucleus, olfactory tubercle, shell of nucleus accumbens, claustrum, lateral septum, laterodorsal thalamic, medial habenular, subthalamic, reuniens thalamic nuclei, subiculum, periaqueductal grey matter and pons. A lower binding site density was observed in the anterior and medial hippocampus, olfactory bulb, caudate putamen, the core of the nucleus accumbens, medial septum, ventrolateral, ventroposterolateral and mediodorsal thalamic nuclei, lateral and medial geniculate nuclei, hypothalamic area, substantia nigra, ventral tegmentum area and interpedoncular nucleus. A moderate and similar labelling was found in the dorsal and ventral horn of the spinal cord. No labelling was apparent in the corpus callosum. Thus, it appears that the ORL1 receptor is particularly abundant in the cerebral cortex, limbic system of the rat brain and some areas involved in pain perception.
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PMID:Autoradiographic localization of [3H]nociceptin binding sites in the rat brain. 1103 85

Nociceptin-orphanin FQ (OFQ/N) is a newly discovered peptide involved in pain transmission. The method is described to identify metabolic pathway of this neuropeptide in the spinal cord of rats using capillary size-exclusion liquid chromatography coupled to electrospray ionization mass spectrometry. The applied technique is rapid and selective, and allows for simultaneous measurement and quantitation of several fragments in the incubation mixture.
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PMID:Determination of nociceptin-orphanin FQ metabolites by capillary LC-MS. 1108 62

The aim of the present study was to examine the effect of microinjection of orphanin FQ (OFQ) into periaqueductal gray (PAG) on sensory processing in the wide dynamic range (WDR) neurons of the spinal dorsal horn and to explore the effect of OFQ on a descending system of pain modulation. The results show that microinjection of OFQ into ipsilateral PAG significantly facilitated C-fibre evoked response and post-discharge of spinal dorsal horn WDR neurons. This is consistent with our previous results obtained in behavioral studies. It suggests that the supraspinal effect of OFQ on pain may partly be mediated by PAG neurons.
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PMID:Effects of microinjection of OFQ into PAG on spinal dorsal horn WDR neurons in rats. 1114 64

It is now well established that the analgesic actions of opioids can be modified by "anti-analgesic" or "antiopioid" peptides, among them cholecystokinin (CCK). Although the focus of much recent work concerned with CCK-opioid interactions has been at the level of the spinal cord, CCK also acts within the brain to modify opioid analgesia. The aim of the present study was to characterize the actions of CCK in a brain region in which the circuitry mediating the analgesic actions of opioids is relatively well understood, the rostral ventromedial medulla (RVM). Single-cell recording was combined with local infusion of CCK in the RVM and systemic administration of morphine in lightly anesthetized rats. The tail-flick reflex was used as a behavioral index of nociceptive responsiveness. Two classes of RVM neurons with distinct responses to opioids have been identified. OFF cells are activated, indirectly, by morphine and mu-opioid agonists, and there is strong evidence that this activation is crucial to opioid antinociception. ON cells, thought to facilitate nociception, are directly inhibited by opioids. Cells of a third class, NEUTRAL cells, do not respond to opioids, and whether they have any role in nociceptive modulation is unknown. CCK microinjected into the RVM by itself had no effect on tail flick latency or the firing of any cell class but significantly attenuated opioid activation of OFF cells and inhibition of the tail flick. Opioid suppression of ON-cell firing was not significantly altered by CCK. Thus CCK acting within the RVM attenuates the analgesic effect of systemically administered morphine by preventing activation of the putative pain inhibiting output neurons of the RVM, the OFF cells. CCK thus differs from another antiopioid peptide, orphanin FQ/nociceptin, which interferes with opioid analgesia by potently suppressing all OFF-cell firing.
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PMID:Circuitry underlying antiopioid actions of cholecystokinin within the rostral ventromedial medulla. 1115 27

Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two neuropeptides derived from the same precursor protein that exhibit opposing effects on spinal neurotransmission and nociception. Here, we have used whole-cell, patch-clamp recordings from visually identified neurons in spinal cord dorsal horn slices of genetically modified mice to investigate the role of the N/OFQ receptor (N/OFQ-R) in the modulatory action of both peptides on excitatory glutamatergic and inhibitory glycinergic and gamma-aminobutyric acid (GABA)-ergic synaptic transmission. In wild-type mice, N/OFQ selectively suppressed excitatory transmission in a concentration-dependent manner but left inhibitory synaptic transmission unaffected. In contrast, NST reduced only inhibitory but not alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated excitatory synaptic transmission. N/OFQ-mediated inhibition of excitatory transmission was completely absent in N/OFQ-R receptor-deficient (N/OFQ-R(-/-)) mice and significantly reduced in heterozygous (N/OFQ-R(+/-)) mice, whereas the action of NST on inhibitory neurotransmission was completely retained. To test for the relevance of these results for spinal nociception, we investigated the effects of intrathecally injected N/OFQ in the mouse formalin test, an animal model of tonic pain. N/OFQ (3 nmol/mouse) induced significant antinociception in wild-type mice, but had no antinociceptive effects in N/OFQ-R(-/-) mice. These results indicate that the inhibitory action of N/OFQ on excitatory glutamatergic synaptic transmission and its spinal antinociceptive action are mediated via the N/OFQ receptor, whereas the action of NST is independent of this receptor.
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PMID:Modulation of synaptic transmission by nociceptin/orphanin FQ and nocistatin in the spinal cord dorsal horn of mutant mice lacking the nociceptin/orphanin FQ receptor. 1117 57

The nociceptin receptor (Noci-R) is a G protein-coupled receptor present in neural tissues and its activation by nociceptin is involved in the processing of pain signals. Here, we report that Noci-R is present and functional on peripheral blood polymorphonuclear leukocytes (PMN). Human PMN express mRNA for Noci-R, its nucleotide sequence determined, and specific binding with [(125)I]-labeled nociceptin gave an apparent K(d) approximately 1.5 nM for this PMN opioid receptor. Nociceptin evoked PMN chemotaxis with maximal activity at 100 pM, without intracellular Ca(2+) mobilization. When injected in murine air pouches, nociceptin elicited leukocyte infiltration in a concentration-dependent fashion. Nociceptin-stimulated PMN infiltration was inhibited by treating mice with a synthetic analog of the aspirin-triggered lipid mediator 15-epi-lipoxin A(4). The present results identify nociceptin as a potent chemoattractant and provide a novel link between the neural and immune systems that are blocked by aspirin-triggered lipid mediators and may be relevant in neurogenic inflammation.
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PMID:Cutting edge: nociceptin stimulates neutrophil chemotaxis and recruitment: inhibition by aspirin-triggered-15-epi-lipoxin A4. 1123 2

Orphanin FQ (OFQ) is a newly-discovered neuropeptide which shares great similar sequence with endogenous opioid peptide but with different functions. The present study was to investigate the role of OFQ microinjected in the periaqueductal gray (PAG) on pain threshold and acupuncture analgesia (AA) using tail flick tests. The results show that the hyperalgesia of OFQ and its antagonization on AA in PAG are dose-related. OFQ in PAG decreases the enhancing effect on AA induced by ohmefentanyl, a selective mu-receptor agonist. These observations suggest that OFQ in PAG can increase the rat pain sensitivity and antagonize AA.
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PMID:[Effect of orphanin FQ on acupuncture analgesia and noxious stimulation in the periaqueductal gray]. 1132 65

The aim of the present study was to observe the alternation of central orphanin FQ (OFQ, also known as nociceptin) system while electroacupuncture (EA) combined with melatonin (MEL). The experiments were carried out to investigate the changes of OFQ-like immunoreactivity and prepro-orphanin FQ (ppOFQ) mRNA in some certain nuclei of the rat brain. Using immunohistochemical technique we found that the level of OFQ-like immunoreactivity was increased significantly in some pain-modulation-related nuclei, such as ventromedial hypothalamic nucleus, raphe magnus nucleus, dorsal raphe nucleus and periaqueductal gray (PAG) after intraperitoneal (i.p.) injection of MEL 60 mg/kg, and it was further enhanced while MEL combined with EA. By using in situ hybridization, we found that ppOFQ mRNA expression was decreased in the same nuclei after the administration of MEL, and further decreased following the combination of EA and MEL. The results suggested that attenuating the release and synthesis of OFQ in the brain is one of the mechanisms that melatonin promotes acupuncture analgesia.
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PMID:Alteration of orphanin FQ immunoreactivity and ppOFQ mRNA by combination of melatonin with electroacupuncture. 1139 93


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