Involvement of central μ-opioid system in the scratching behavior in mice, and the suppression of it by the activation of κ-opioid system

Umeuchi, Hideo; Togashi, Yuko; Honda, Toshiyuki; Nakao, Kaoru; Okano, Kiyoshi; Tanaka, Toshiaki; Nagase, Hiroshi

doi:10.1016/j.ejphar.2003.08.007

Cited by 135 publications

(89 citation statements)

References 39 publications

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“…-Agonists have been shown to block the itching response of morphine through a central effect (13,21) while maintaining or enhancing morphine-induced antinociception. This anti-pruritic effect may be due to a direct effect in one or more areas of the brain and/or a positive feedback from the skin at the level of the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

“…-Opioid receptor agonists elicit itching from their central nervous system actions (13,19), and this activity may be due to disinhibition of the central itch response that occurs as a result of their antinociceptive action (20).…”

Section: Discussionmentioning

confidence: 99%

“…-Opioid stimulation inhibits -receptor effects both centrally and peripherally (11). Nalfurafine, a new -opioid receptor agonist, was effective in reducing the scratching behavior induced by an injection of substance P in the mouse model (13,14). From these findings, it was hypothesized that uremic pruritus could be triggered and sustained by the release of substance P (15).…”

mentioning

confidence: 99%

“…-Opioid receptor antagonists can inhibit itching induced by substance P (13). -Opioid stimulation inhibits -receptor effects both centrally and peripherally (11).…”

mentioning

confidence: 99%

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κ-Opioid System in Uremic Pruritus

Wíkström

Gellert²,

Ladefoged³

et al. 2005

Journal of the American Society of Nephrology

271

170

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Uremic pruritus is a very common and frustrating condition for both patients and clinicians because no treatment has been demonstrated to be effective in relieving the itch. In this report, nalfurafine, a new -opioid receptor agonist, was used to treat uremic pruritus in patients who were undergoing routine hemodialysis. Two multicenter, randomized, double-blind, placebocontrolled studies enrolled 144 patients with uremic pruritus to postdialysis intravenous treatment with either nalfurafine or placebo for 2 to 4 wk. A meta-analysis approach was used to assess the efficacy of nalfurafine. Statistically significant reductions in worst itching (P ‫؍‬ 0.0212), itching intensity (P ‫؍‬ 0.0410), and sleep disturbances (P ‫؍‬ 0.0003) were noted in the nalfurafine group as compared with placebo. Improvements in itching (P ‫؍‬ 0.0025) and excoriations (P ‫؍‬ 0.0060) were noted for the nalfurafine-treated patients. Nalfurafine showed similar types and incidences of drug-related adverse events as did placebo. Nalfurafine was shown to be an effective and safe compound for use in this severely ill patient population. U remic pruritus has a major impact on the quality of life in patients who already have a compromised lifestyle (1-5). It is, of itself, not a life-threatening condition; however, it is known to contribute to an increase in morbidity (6) and mortality (7) of uremic patients. The only current definitive treatment for uremic pruritus is successful renal transplantation (8). Increasing the dialysis dose as well as implementing other therapeutic measures to lessen the symptoms, some as extraordinary as acupressure, (9) have provided only limited effectiveness in dialysis patients.Stimulation of the -opioid receptor in the brain and/or peripheral nerve endings by its agonists, such as morphine, can result in itching (10 -12). -Opioid receptor antagonists can inhibit itching induced by substance P (13). -Opioid stimulation inhibits -receptor effects both centrally and peripherally (11). Nalfurafine, a new -opioid receptor agonist, was effective in reducing the scratching behavior induced by an injection of substance P in the mouse model (13,14). From these findings, it was hypothesized that uremic pruritus could be triggered and sustained by the release of substance P (15). This led to the studies in the treatment of uremic pruritus using nalfurafine. Materials and Methods Study Design and TreatmentsTwo multicenter, randomized, double-blind, placebo-controlled clinical studies were performed with the common objective of assessing the efficacy and the safety of nalfurafine, as compared with placebo, in the treatment of uremic pruritus. The inclusion and exclusion criteria and the evaluations, methods of evaluations, and times of evaluations were the same in both studies.Patients were males and females who were at least 18 yr of age and undergoing routine hemodialysis secondary to ESRD and had severe, uncontrolled pruritus caused only by ESRD. Female patients were not of childbearing potential or were using an acceptab...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…-Opioid receptor antagonists can inhibit itching induced by substance P (13). -Opioid stimulation inhibits -receptor effects both centrally and peripherally (11).…”

mentioning

confidence: 99%

See 2 more Smart Citations

κ-Opioid System in Uremic Pruritus

Wíkström

Gellert²,

Ladefoged³

et al. 2005

Journal of the American Society of Nephrology

271

170

View full text Add to dashboard Cite

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“…The antiscratching activity of TRK-820 with ED 50 7.3 g/kg was antagonized by nor-BNI (Togashi et al, 2002). TRK-820 was effective in scratching induced by the other pruritogenic substances: substance P (Togashi et al, 2002;Umeuchi et al, 2003;Utsumi et al, 2004), chloroquine (Inan & Cowan, 2004), compound 48/80 (Wang, Y et al, 2005), agmatin (Inan & Cowan, 2006a), and 5'-GNTI (Inan et al, 2009a(Inan et al, , 2011 (Table 8). 5'-GNTI-induced scratching was suppressed by both pretreatment and post-treatment with TRK-820.…”

Section: Antipruritic Effects 41 Preclinical Studiesmentioning

confidence: 99%

Opioid Kappa Receptor Selective Agonist TRK-820 (Nalfurafine Hydrochloride)

Fujii¹,

Hirayama²,

Nagase³

2012

Pharmacology

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Pruritus, Prurigo and Lichen Simplex

Ständer

Greaves

2016

Rook's Textbook of Dermatology, Ninth Edition

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Chronic pruritus (of more than 6 weeks duration) is one of the most frequent and burdensome of symptoms, occurring not only in association with a variety of dermatoses but also in other medical specialities, such as neurology, gynaecology and psychiatry. Prurigo nodularis and lichen simplex are characterized by a vicious circle of repeated scratching and pruritus, and represent cutaneous reaction patterns with a high negative impact on patients' quality of life. During the past two decades, new insights have been gained on specific neurons, receptors and mediators that are exclusively involved in the mediation of pruritus and not of pain. Diagnostic work‐up of chronic pruritus, prurigo nodularis and lichen simplex is challenging and time‐consuming, and management of the conditions remains difficult and unsatisfactory. The mainstays of treatment to date are antihistamines, anticonvulsants and certain antidepressants. Better understanding of the underlying pathophysiology of pruritus has enabled novel treatment approaches that target the pruritus‐specific mechanisms. Current knowledge on treatment is summarized for the first time in the European Guideline on Chronic Pruritis.

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Involvement of central μ-opioid system in the scratching behavior in mice, and the suppression of it by the activation of κ-opioid system

Cited by 135 publications

References 39 publications

κ-Opioid System in Uremic Pruritus

κ-Opioid System in Uremic Pruritus

Opioid Kappa Receptor Selective Agonist TRK-820 (Nalfurafine Hydrochloride)

Pruritus, Prurigo and Lichen Simplex

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