ArticlePsychopharmacology2018
Dissociable effects of the kappa opioid receptor agonist nalfurafine on pain/itch-stimulated and pain/itch-depressed behaviors in male rats.
Article in Psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Kappa opioids suppress histaminergic itch by inhibiting mediodorsal thalamus-projecting claustrum glutamatergic neurons.Science advances · 2026Article
- Effects of repeated nalfurafine and VZTK35 treatments on fentanyl/cocaine mixture self-administration in a rat drug-vs.-food choice procedure.Psychopharmacology · 2026Article
- Nalfurafine is Aversive at Antinociceptive Doses in Mice.Pharmacology research & perspectives · 2025Article
- Nalfurafine reverses fentanyl-induced muscle rigidity and respiratory depression without affecting sedation in rats: decoupling respiration from sedation.Journal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- Review
- Effects of Selective and Mixed-Action Kappa and Delta Opioid Receptor Agonists on Pain-Related Behavioral Depression in Mice.Molecules (Basel, Switzerland) · 2024Article
- Systematic Structure-Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially Nonaddictive Pain Management Treatments.Journal of medicinal chemistry · 2024Article
- Quantification of observable behaviors following oral administration of oxycodone and nalfurafine in male rhesus monkeys.Drug and alcohol dependence · 2023Article
- Characterization of a Potential KOR/DOR Dual Agonist with No Apparent Abuse Liability via a Complementary Structure-Activity Relationship Study on Nalfurafine Analogues.ACS chemical neuroscience · 2022Article
- Difelikefalin in the Treatment of Chronic Kidney Disease-Associated Pruritus: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Lack of effect of the nociceptin opioid peptide agonist Ro 64-6198 on pain-depressed behavior and heroin choice in rats.Drug and alcohol dependence · 2022Article
- Molecular Genetics of Kappa Opioids in Pain and Itch Sensations.Handbook of experimental pharmacology · 2022Review
- Preclinical Studies on Nalfurafine (TRK-820), a Clinically Used KOR Agonist.Handbook of experimental pharmacology · 2022Article
- The kappa-opioid receptor agonist, triazole 1.1, reduces oxycodone self-administration and enhances oxycodone-induced thermal antinociception in male rats.Psychopharmacology · 2021Article
- Effects of kappa opioid receptor agonists on fentanyl vs. food choice in male and female rats: contingent vs. non-contingent administration.Psychopharmacology · 2021Article
- Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch.Frontiers in pharmacology · 2021Article
- Mechanisms Underlying the Anti-Suicidal Treatment Potential of Buprenorphine.Advances in drug and alcohol research · 2021Article
- Effects of repeated treatment with monoamine-transporter-inhibitor antidepressants on pain-related depression of intracranial self-stimulation in rats.Psychopharmacology · 2020Article
- Quantification of observable behaviors induced by typical and atypical kappa-opioid receptor agonists in male rhesus monkeys.Psychopharmacology · 2020Article
- Functional Selectivity and Antinociceptive Effects of a Novel KOPr Agonist.Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleNalfurafine is a G protein signaling-biased kappa opioid receptor (KOR) agonist approved in Japan for second-line treatment of uremic pruritus. Neither nalfurafine nor any other KOR agonist is currently approved anywhere for treatment of pain, but recent evidence suggests that G protein signaling-biased KOR agonists may have promise as candidate analgesics/antipruritics with reduced side effects compared to nonbiased or ß-arrestin-signaling-biased KOR agonists.
objectivesThis study compared nalfurafine effects in rats using assays of pain-stimulated and pain-depressed behavior used previously to evaluate other candidate analgesics. Nalfurafine effects were also examined in complementary assays of itch-stimulated and itch-depressed behavior.
methodsIntraperitoneal lactic acid (IP acid) and intradermal serotonin (ID 5HT) served as noxious and pruritic stimuli, respectively, in male Sprague Dawley rats to stimulate stretching (IP acid) or scratching (ID 5HT) or to depress positively reinforced operant responding in an assay of intracranial self-stimulation (ICSS; both stimuli).
resultsNalfurafine was equipotent to decrease IP acid-stimulated stretching and ID 5HT-stimulated scratching; however, doses of nalfurafine that decreased these pain/itch-stimulated behaviors also decreased control ICSS performance. Moreover, nalfurafine failed to alleviate either IP acid- or ID 5HT-induced depression of ICSS.
conclusionsThese results suggest that nalfurafine-induced decreases in pain/itch-stimulated behaviors may reflect nonselective decreases in motivated behavior rather than analgesia or antipruritus against the noxious and pruritic stimuli used here. This conclusion agrees with the absence of clinical data for nalfurafine analgesia and the weak clinical data for nalfurafine antipruritus. Nalfurafine bias for G protein signaling may not be sufficient for clinically safe and reliable analgesia or antipruritus.
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