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

Pruritus occurs frequently following opioid use, particularly after neuraxial administration. Although not life threatening, pruritus is discomforting and may decrease patient satisfaction. Even though the mechanism of opioid-induced pruritus is not yet fully understood, there is increasing evidence of the important role played by micro opioid receptors. Animal experiments pointing to the role of the micro opioid receptor and the efficacy of micro opioid receptor antagonists for opioid adverse effect prophylaxis and treatment have been replicated in several studies. Serotonin and dopamine D(2) receptors, prostaglandins and spinal inhibitory pathways may also be involved in the genesis of pruritus. Several pharmacological agents have been used both for the treatment of established pruritus and in its prevention. Of these, micro opioid receptor antagonists have been most consistent in terms of attenuating opioid-induced pruritus but present problems in dose and administration. Other drugs, including mixed opioid receptor agonist-antagonists, serotonin 5-HT(3) receptor antagonists, propofol, NSAIDs and D(2) receptor antagonists, have also been demonstrated to be useful. This review summarises the current understanding of the mechanisms causing opioid-induced pruritus and the pharmacological therapies available to prevent and/or manage this disorder.
 ...
PMID:Pathophysiology and management of opioid-induced pruritus. 1798 54

The common adverse effect of centrally-injected mu-opioid receptor (mu-OR) agonists is pruritus. This study was conducted using mice to examine whether different subtypes of mu-OR would be responsible for pruritus and analgesia. Intracisternal injections of morphine and morphine-6beta-glucronide (M6G), but not M3G, produced an antinociceptive effect. Morphine, but neither M6G nor M3G, induced facial scratching, a pruritus-related response. Facial scratching following morphine was not affected by the mu(1)-OR antagonist naloxonazine at doses that inhibited the antinociceptive effects. The results suggest that different subtype and/or splice variants of mu-OR are separately involved in pruritus and antinociception of opioids.
 ...
PMID:Evidence for separate involvement of different mu-opioid receptor subtypes in itch and analgesia induced by supraspinal action of opioids. 1840 1

Arterial vasodilation with concomitant hyperdynamic circulation is a common finding in cirrhotic subjects. Elevated levels of plasma endogenous opioid peptides have been reported in cholestasis and cirrhosis. Increased opioid peptides contribute to different manifestations of chronic liver disease such as pruritus, ascitis, and hepatic encephalopathy. In this study the potential role of opioid system in cirrhosis-induced vascular hyporesponsiveness was investigated. Bile duct ligated and sham operated animals received daily subcutaneous administration of naltrexone, an opioid receptor antagonist (20 mg/kg/day), or saline for 28 days. After 4 weeks the superior mesenteric artery was cannulated and was perfused according to McGregor method and then phenylephrine vasoconstrictor response of mesenteric vessels (10(-10) to 10(-6 )mol) was examined. In order to evaluate the effects of acute opioid receptor blockade, additional groups of animals were treated by acute single intraperitoneal naltrexone injection (20 mg/kg). Plasma level of nitrite/nitrate as an indicator for nitric oxide production was measured. Biliary cirrhosis was accompanied with a decrease in baseline perfusion pressure in mesenteric vascular bed (P < 0.01). Chronic opioid receptor blockade significantly increased this parameter (P < 0.01). The maximum pressure response to phenylephrine was decreased significantly in cirrhosis while chronic naltrexone treatment completely improved it (P < 0.01). Acute single injection of naltrexone could not influence the understudied homodynamic parameters. Chronic opioid receptor blockade did not modulate the increased nitrite/nitrate levels following cholestasis. This study provided evidence on the contribution of endogenous opioid system to vascular hyporesponsiveness in cirrhosis which is not directly correlated to high plasma NO levels.
 ...
PMID:Opioid receptor blockade improves mesenteric responsiveness in biliary cirrhosis. 1846 46

In atopic dermatitis patients, pruritus is a severe symptom that is difficult to treat. It is previously reported that TRK-820, a kappa-opioid receptor agonist, reduces murine scratching behavior induced by an intradermal injection of histamine or substance P or an intracisternal injection of morphine. It is also reported that TRK-820 ameliorates the intractable pruritus in hemodialysis patients. However, it is still unclear whether TRK-820 possesses antipruritic effects on the pruritus in dermatitis patients. Therefore, the effect of TRK-820 on scratching behavior in NC/Nga mice maintained in a conventional environment, an animal model of atopic dermatitis, was examined. Oral TRK-820 (10-100 microg/kg) inhibited the scratching behavior but did not affect the locomotor activity. On the other hand, ketotifen (3-30 mg/kg, po), an antihistamine, did not attenuate the scratching behavior. TRK-820 showed the highest selectivity and activity for kappa-opioid receptor among all human opioid receptors. Release of various inflammatory mediators from a variety of cells and activity of nitric oxide synthase were not altered by TRK-820. This compound showed much lower affinities for other receptors than that for opioid receptors. These results suggest that TRK-820 is effective against antihistamine-resistant pruritus in atopic dermatitis patients via the kappa opioid receptor.
 ...
PMID:[Effect of TRK-820, a selective kappa opioid receptor agonist, on scratching behavior in an animal model of atopic dermatitis]. 1851 86

The recent approval by the US Food and Drug Administration of 2 medications--methylnaltrexone and alvimopan--introduces a new class of therapeutic entities to clinicians. These peripherally acting mu-opioid receptor antagonists selectively reverse opioid actions mediated by receptors outside the central nervous system, while preserving centrally mediated analgesia. Methylnaltrexone, administered subcutaneously, has been approved in the United States, Europe, and Canada. In the United States, it is indicated for the treatment of opioid-induced constipation in patients with advanced illness (eg, cancer, AIDS) who are receiving palliative care, when response to laxative therapy has not been sufficient. Alvimopan, an orally administered medication, has been approved in the United States to facilitate recovery of gastrointestinal function after bowel resection and primary anastomosis. Clinical and laboratory studies performed during the development of these drugs have indicated that peripheral receptors mediate other opioid effects, including decreased gastric emptying, nausea and vomiting, pruritus, and urinary retention. Laboratory investigations with these compounds suggest that opioids affect fundamental cellular processes through mechanisms that were previously unknown. These mechanisms include modifications of human immunodeficiency virus penetration, tumor angiogenesis, vascular permeability, and bacterial virulence.
 ...
PMID:Development of peripheral opioid antagonists' new insights into opioid effects. 1882 66

Pruritus is an enigmatic, seriously disabling symptom accompanying cholestatic liver diseases and a broad range of other disorders. Most recently, novel itch-specific neuronal pathways, itch mediators and their relevant receptors have been identified. In addition, new antipruritic therapeutic strategies have been developed and/or are under evaluation. This review highlights recent experimental and clinical findings focusing on the pathogenesis and actual treatment of pruritus in cholestatic liver disease. Evidence-based therapeutic recommendations, including the use of anion exchange resins cholestyramine, colestipol and colesevelam, the microsomal enzyme inducer rifampicin, the opioid receptor antagonists naltrexone and naloxone, and the serotonin reuptake inhibitor sertraline, are provided.
 ...
PMID:Pathogenesis and treatment of pruritus in cholestasis. 1884 5

Itch/pruritus is the most common side effect associated with spinal administration of morphine given to humans for analgesia. The aim of this study was to investigate the effectiveness of kappa-opioid receptor (KOR) agonists with diverse chemical structures as antipruritics and to elucidate the receptor mechanism underlying the antipruritic effect in monkeys. In particular, previously proposed non-KOR-1 agonists, including nalfurafine [TRK-820, 17-cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 beta-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan], bremazocine [(+/-)-6-ethyl-1,2,3,4,5,6-hexahydro-3-[(1-hydroxycyclopropy)-methyl]-11,11-dimethyl-2,6-methano-3-benzazocin-8-ol], and GR 89696 [4-[(3,4-dichlorophenyl)acetyl]-3-(1-pyrrolidinylmethyl)-1-piperazinecarboxylic acid methyl ester] were studied in various behavioral assays for measuring itch/scratching, analgesia, and respiratory depression. Systemic administration of nalfurafine (0.1-1 microg/kg), bremazocine (0.1-1 microg/kg), or GR 89696 (0.01-0.1 microg/kg) dose-dependently attenuated intrathecal morphine (0.03 mg)-induced scratching responses without affecting morphine antinociception. The combination of intrathecal morphine with these KOR agonists did not cause sedation. In addition, pretreatment with effective antiscratching doses of nalfurafine, bremazocine, or GR 89696 did not antagonize systemic morphine-induced antinociception and respiratory depression. The dose-addition analysis revealed that there is no subadditivity for nalfurafine in combination with morphine in the antinociceptive effect. Furthermore, the KOR antagonist study revealed that antiscratching effects of both nalfurafine and a prototypical KOR-1 agonist, U-50488H [trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide], could be blocked completely by a selective KOR antagonist, nor-binaltorphimine (3 mg/kg). These findings suggest that the agonist action on KOR mainly contributes to the effectiveness of these atypical KOR agonists as antipruritics, and there is no evidence for KOR subtypes or mu-opioid antagonist action underlying the effects of these KOR agonists. This mechanism-based study further supports the clinical potential of KOR agonists as antipruritics under the context of spinal opioid analgesia.
 ...
PMID:Effects of atypical kappa-opioid receptor agonists on intrathecal morphine-induced itch and analgesia in primates. 1884 4

The present study was conducted to determine whether cutaneous itch involves mu-opioid receptors in either of the spinal cord or lower brainstem or in both regions in mice. An intraplantar injection of serotonin hydrochloride (100 nmol/site) induced biting, an itch-related behavior. The behavior was inhibited by subcutaneous (0.3-1 mg/kg) and intracisternal (1--10 nmol/site), but not intrathecal (1--10 nmol/site), injections of naloxone hydrochloride. An intradermal injection of serotonin (100 nmol/site) to the rostral back induced scratching, an itch-related behavior, which was inhibited by subcutaneous (1 mg/kg) and intracisternal (10 nmol/site) injections of naloxone. These results suggest that mu-opioid receptor in the lower brainstem, but not spinal cord, is a site of central pruritogenic action of opioids and is involved in the facilitatory regulation of itch signaling.
 ...
PMID:Intracisternal, but not intrathecal, injection of naloxone inhibits cutaneous itch-related response in mice. 1898 88

Pruritus (itch) is an unpleasant sensation inducing the desire to scratch. Chronic pruritus (>6 weeks' duration) is a major and distressing symptom of many diseases of dermatological, systemic, neurological or psychogenic origin. Frequently, the underlying cause of pruritus cannot be identified and causal therapy is not possible. Furthermore, chronic pruritus is frequently refractory to conventional symptomatic therapies. Recent research has revealed new neuronal mechanisms in the skin and brain, suggesting novel therapeutic targets. The efficacy of the corresponding innovative therapies has been proven in recent studies and case series. For example, topical or systemic application of specific agonists such as cannabinoids or calcineurin inhibitors can influence neuroreceptors on sensory nerve fibers of the skin and suppress pruritus. Itch-selective neurons in the dorsal horn of the spinal cord can be targeted to inhibit the transmission of pruritus to the somatosensory cortex. Anticonvulsants, antidepressants and micro-opioid receptor antagonists interfere with the sensation of pruritus in the central nervous system. Chronic pruritus of any origin leads to considerable psychosocial burden and impairs quality of life. Psychoeducational interventions, stress training, training in social competence and relaxation techniques are therefore important elements in the treatment of chronic pruritus. Increasing knowledge of the neurobiology of chronic pruritus offers new therapeutic strategies. Currently, several clinical trials are investigating the efficacy of new substances addressing neuroreceptors and cytokines in the skin and central nervous system. The present review aims to provide an overview of current neurophysiological and neurochemical therapeutic models in chronic pruritus.
 ...
PMID:Chronic pruritus: targets, mechanisms and future therapies. 1922 35

Pruritus is a common complication of end-stage renal disease (ESRD), affecting about one-third of dialysis patients. It is a chronic, unpleasant symptom with a strong negative impact on patients' quality of life, often inducing sleeplessness and mood disorders. Recent data show that it is also associated with increased mortality. The pathogenesis of uraemic pruritus (UP) is multifactorial. Triggering factors may include uraemia-related abnormalities (particularly involving calcium, phosphorus and parathyroid hormone metabolism), accumulation of uraemic toxins, systemic inflammation, cutaneous xerosis, and common co-morbidities such as diabetes mellitus and viral hepatitis. Recent findings suggest that the neurophysiology of itch is similar to that of pain; this has led to the hypothesis that the two phenomena also closely interact in ESRD patients, who often also experience uraemic neuropathy. The management of UP needs to address several different issues, such as optimization of dialysis efficacy and skin hydration, and correction of calcium-phosphorus metabolism abnormalities. A wide range of antipruritic drugs have been suggested for the treatment of UP, although most of them have only been tested in small, uncontrolled trials, which have yielded conflicting results. Antihistamines are now known to have little or no efficacy, although they are still often prescribed. Novel neurotropic drugs such as gabapentin, along with opioid receptor modulators such as nalfurafine, appear to be effective and well tolerated, but their efficacy has not yet been directly compared. Finally, physical therapies, including UV radiation, may also have a role in patients with refractory symptoms.
 ...
PMID:Uraemic pruritus: clinical characteristics, pathophysiology and treatment. 1927 70


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