Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the possibility that scratching induced by norbinaltorphimine, a selective kappa-opioid receptor antagonist, is due to an itch sensation, using compound 48/80 as control pruritogenic agent. When norbinaltorphimine was injected s.c. into the rostral back, mice scratched the skin around the injection site with their hind paws. Although the intensity of the scratching could not be compared because the dose and injection route were different, the character and time course of the scratching behavior induced by compound 48/80 injected i.d. were similar to those with norbinaltorphimine. The scratching behavior induced by norbinaltorphimine was dose-dependently and significantly inhibited by pretreatment with chlorpheniramine. Compound 48/80-induced scratching was also dose-dependently and significantly inhibited by p.o. pretreatment with chlorpheniramine. The scratching behavior induced by norbinaltorphimine was dose-dependently and significantly inhibited by pretreatment with U-50,488H (trans-(+/-)-2-(3,4-dichlorophenyl)-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] acetamide methansulfonate), a kappa-opioid receptor agonist. Unexpectedly, the scratching behavior induced by compound 48/80 was also dose-dependently and significantly reduced by pretreatment with U-50,488H. These results suggest that the injection of norbinaltorphimine into the rostral back of the mouse elicited scratching, which may be an itch-associated response. Furthermore, the scratching behavior produced by norbinaltorphimine may be due in part to the release of histamine followed by antagonism of kappa-opioid receptors.
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PMID:Norbinaltorphimine, a selective kappa-opioid receptor antagonist, induces an itch-associated response in mice. 1133 76

The effects of the kappa-opioid receptor agonist, TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, on the itch sensation were compared with those of histamine H1 receptor antagonists, using the mouse pruritogen-induced scratching model. Peroral administration of TRK-820 reduced the numbers of substance P- or histamine-induced scratches dose dependently. No obvious suppression of the spontaneous locomotor activity was observed at the doses used for the experiments, indicating that the inhibition of scratches was not due to the effect on general behavior. Furthermore, the scratching inhibitory activity of TRK-820 was dose dependently antagonized by the specific kappa-opioid receptor antagonist, nor-binaltorphimine, suggesting that the inhibitory activity was mediated via kappa-opioid receptors. Histamine H1 receptor antagonists, chlorpheniramine and ketotifen, did not inhibit substance P-induced scratches, or did so only partially. Both antihistamines inhibited the histamine-induced scratches completely. These results suggest that TRK-820 has antipruritic activity which is mediated by kappa-opioid receptors, and is effective in both antihistamine-sensitive and -resistant pruritus.
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PMID:Antipruritic activity of the kappa-opioid receptor agonist, TRK-820. 1182 Oct 35

Loperamide and three of its analogs were evaluated for their ability to inhibit binding to cloned human opioid receptor subtypes and to produce antipruritus and antinociception following local s.c. administration to rodents. All four compounds were fully efficacious agonists with affinities of 2 to 4 nM for the cloned human mu opioid receptor. Local s.c. injection of loperamide, ADL 01-0001 or ADL 01-0002 at the same site as the introduction of the pruritogenic compound 48/80 resulted in antipruritic activity in a mouse model of itch. Similarly, i.paw or i.pl. administration of compounds ADL 01-0001, ADL 01-0002 and ADL 01-0003 to inflamed paws caused potent antinociception, inhibiting late phase formalin-induced flinching, Freund's adjuvant-induced mechanical hyperalgesia and tape stripping-induced mechanical hyperalgesia. Loperamide and its analogs were efficacious in animal models of itch and inflammatory pain, and may have potential therapeutic utility as antipruritic and antihyperalgesic agents.
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PMID:Antipruritic and antihyperalgesic actions of loperamide and analogs. 1238 84

Opioid peptides are endogenous neuromodulators that play a major role in the nociceptive pathway by interacting with opioid receptors. So far, four opioid receptors (micro-, delta-, kappa-, orphan-receptor) have been cloned with a wide distribution in the central and peripheral nervous system. In the present study, we give first evidence for the presence of the micro-opioid receptor (MOR) isoform 1A in nerve fibers of human skin. Immunohistochemical analysis revealed MOR immunoreactivity to be present in dermal and epidermal nerve fibers. Double-immunofluorescence staining revealed that MOR is present on calcitonin gene-related protein (CGRP)-positive sensory nerve fibers, while autonomic nerves of blood vessels, hair follicles, or skin glands were negative. In diseased skin such as psoriasis vulgaris, atopic dermatitis, and prurigo nodularis, distribution of MOR 1A immunoreactivity was similar to that of normal skin. These findings expand our knowledge about a direct regulatory role of cutaneous opioid receptors in the skin. Thus, peripheral cutaneous opioid receptors may be involved in the transmission of pain and pruritus, respectively. This is supported by previous observation that opioid receptor antagonists may significantly diminish experimentally evoked histamine-induced itch of the skin. Together, our findings contribute to the understanding of the high antipruritic potency of opioid receptor antagonists in various skin and systemic diseases.
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PMID:Localization of mu-opioid receptor 1A on sensory nerve fibers in human skin. 1246 12

Pruritus (itch sensation) is the most common side effect associated with spinal administration of morphine given to humans for analgesia. A variety of agents have been proposed as antipruritics with poorly understood mechanisms and they are effective with variable success. kappa-Opioid agonists possess several actions that are opposite to micro -opioid agonists. We proposed to investigate the role of kappa-opioid receptors (KORs) in morphine-induced scratching and antinociception in monkeys. Scratching responses were counted by observers blinded to treatment. Antinociception was measured by a warm water (50 degrees C) tail-withdrawal assay. Pretreatment with low doses of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide (U-50488H) (0.032-0.18 mg/kg s.c.), a selective KOR agonist, dose dependently suppressed the s.c. morphine dose-effect curve for scratching and potentiated s.c. morphine-induced antinociception. In addition, s.c. U-50488H attenuated i.t. morphine (10 and 32 micro g)-induced scratching while maintaining or enhancing i.t. morphine-induced antinociception. The combination of s.c. or i.t. morphine with low doses of U-50488H did not cause sedation. More importantly, pretreatment with 3.2 mg/kg nor-binaltorphimine, a selective KOR antagonist, blocked the effects of s.c. U-50488H on both s.c. and i.t. morphine-induced scratching. These results indicate that activation of KOR attenuates morphine-induced scratching without interfering with antinociception in monkeys. This mechanism-based finding provides functional evidence in support of the clinical potential of KOR agonists as antipruritics in the presence of MOR agonist-induced pruritus.
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PMID:Activation of kappa-opioid receptors inhibits pruritus evoked by subcutaneous or intrathecal administration of morphine in monkeys. 1264 66

The most significant non-systemic side effects of spinal opioids are pruritus, urinary retention and delayed respiratory depression. Pruritus can occur after any opioid, but its incidence may differ with the affinity of the particular opioid to the opioid receptor. Spinal opioid receptors seem to influence urinary retention due to urodynamic effects. Urinary retention can be antagonized by naloxone; however, large doses will also antagonize the analgesic effects. Delayed respiratory depression after spinal opioids is a very rare, but significant complication. In general, respiratory depression after spinal lipophilic opioids will occur earlier than morphine, however the incidence is probably similar. There is some evidence to suggest that the risk of respiratory depression is similar regardless of the route of administration (intramuscular, intravenous, spinal, PCA). Sound knowledge among physicians and nurses, adequate treatment plans, and individual patient selection are essential to avoid significant complications of spinal opioids. If these requirements are fulfilled, most patients can be safely treated with spinal opioids even outside the intensive care unit.
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PMID:[The clinical use of spinal opioids, part 2]. 1279 45

The role of central mu- and kappa-opioid receptors in the regulation of itch sensation was examined using pruritogen-induced mouse scratching behavior model. Intracerebroventricular administration of beta-funaltrexamine, a selective mu-opioid receptor antagonist, inhibited the scratching behavior induced by intradermal substance P, but subcutaneous administration of beta-funaltrexamine did not. Similarly, the scratching inhibitory activity of subcutaneously administered TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, a kappa-opioid receptor agonist, was antagonized by intracerebroventricular administration of nor-binaltorphimine (10 microg/site), a kappa-opioid receptor antagonist, but was not by subcutaneous administration of nor-binaltorphimine. In addition, the scratching induced by the direct activation of central mu-opioid receptor by intracisternal morphine was significantly and dose-dependently inhibited by subcutaneous administration of TRK-820. Taken all together, it is suggested that the central mu-opioid receptors play a role in the processing of itch sensation, and the activation of central kappa-opioid receptors antagonize the central mu-opioid receptor mediated itch processing, thereby suppressing itch sensation.
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PMID:Involvement of central mu-opioid system in the scratching behavior in mice, and the suppression of it by the activation of kappa-opioid system. 1451 95

There is evidence to suggest that the pruritus that results from liver disease is mediated, at least in part, by opioid receptor-ligand interactions; a central component has been proposed. Opiate drugs with agonist activity at opioid receptors induce naloxone-reversible pruritus. Bile acids accumulate in tissues in liver disease. We studied the ability of bile acids to displace specific opioid ligands from opioid receptors in rat and guinea pig brain membrane preparation in binding assays. None of the bile acids studied displaced significantly the opioid ligands from their receptors suggesting that bile acids in vitro are not opioid receptor ligands. The results of this study do not support a role of these bile acids as direct pruritogens by an opioid receptor-mediated mechanism.
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PMID:A study of bile acids as opioid receptor ligands in rat brain membranes. 1501 36

Pruritus (itch sensation) is a significant clinical problem. The aim of this study was to elucidate the roles of opioid receptor types and the site of action in opioid-induced itch in monkeys. Observers who were blinded to the conditions counted scratching after administration of various drugs. Intravenous (i.v.) administration of mu opioid receptor (MOR) agonists (fentanyl, alfentanil, remifentanil, and morphine) evoked scratching in a dose- and time-dependent manner. However, the kappa opioid agonist U-50488H [trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide] and delta opioid agonist SNC80 [(+)-4-[(alphaR)-alpha-[2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-methoxybenzyl]-N,N-diethylbenzamide] did not increase scratching. Intrathecal (i.t.) administration of peptidic MOR agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO, 0.00032-0.01 mg) evoked scratching, but i.v. DAMGO (0.01-1 mg/kg) did not increase scratching. A similar difference between i.t. and i.v. effectiveness was seen with morphine. Antagonist studies revealed that i.v. administration of an opioid receptor antagonist (naltrexone, 0.0032-0.1 mg/kg) dose dependently attenuated scratching induced by i.v. fentanyl (0.018 mg/kg) or morphine (1 mg/kg). However, a peripherally selective opioid antagonist (quaternary naltrexone, 0.0032-0.32 mg/kg) did not block i.v. fentanyl- or morphine-induced scratching. Moreover, a histamine antagonist (diphenhydramine, 0.1-10 mg/kg), failed to attenuate scratching induced by i.t. morphine (0.032 mg) or i.v. morphine (1 mg/kg). Pretreatment with a selective MOR antagonist (clocinnamox, 0.1 mg/kg), but not kappa or delta opioid antagonists (nor-binaltorphimine or naltrindole), blocked i.t. morphine-induced scratching. Together, these data suggest that MOR, not other opioid receptor types or histamine, mediates scratching evoked by opioid analgesics. More important, this study provides in vivo pharmacological evidence that activation of central MOR plays an important role in opioid-induced itch in primates.
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PMID:The role of central mu opioid receptors in opioid-induced itch in primates. 1504 56

Nociceptin, the endogenous peptide ligand for opioid receptor like-1 (ORL1) receptor, has been implicated in the inflammation and pain in the skin. We examined whether nociceptin is a pruritogen in mice. Intradermal injections of nociceptin (1-100 nmol per site) concentration dependently increased scratching in ICR mice; the effect started within 1 min, peaked at 10-20 min, and almost subsided by 30 min. The nociceptin action was absent in ORL1 receptor-deficient (ORL1(-/-)) mice. Systemic, but not local, treatment with naloxone significantly inhibited scratching induced by nociceptin. The action of nociceptin was inhibited by the leukotriene B(4) receptor antagonist ONO-4057 and azelastine, which inhibits the action and production of leukotriene B(4) in the skin. Prepronociceptin and ORL1 receptor mRNAs were substantially expressed in the skin, whereas their expression levels were very low in the dorsal root ganglia. In the skin, nociceptin- and ORL1 receptor-like immunoreactivities were localized in the epidermis. Administration of nociceptin to primary cultures of keratinocytes from ICR and C57BL/6 (ORL1(+/+)) mice, but not ORL1(-/-) mice, produced leukotriene B(4). The results suggest that nociceptin acts on ORL1 receptor on the keratinocytes to produce leukotriene B(4), which induces itch-associated responses in mice.
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PMID:Intradermal nociceptin elicits itch-associated responses through leukotriene B(4) in mice. 1519 60


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