{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T08:05:39Z","timestamp":1783670739618,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T00:00:00Z","timestamp":1431388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["R01-DA032568; R01-AR059193"],"award-info":[{"award-number":["R01-DA032568; R01-AR059193"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"crossref","award":["FAR 2013"],"award-info":[{"award-number":["FAR 2013"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"Background and purpose<\/jats:title>Using an innovative chemical approach, peptide welding technology (PWT<\/jats:styled-content>), a tetrabranched derivative of nociceptin\/orphanin FQ<\/jats:styled-content> (N<\/jats:styled-content>\/OFQ<\/jats:styled-content>) has been generated and pharmacologically characterized. Both in vitro<\/jats:italic> and in vivo<\/jats:italic>\u2005PWT<\/jats:styled-content>2\u2010N<\/jats:styled-content>\/OFQ<\/jats:styled-content> displayed the same pharmacological profile to the natural ligand. It was more potent and produced longer\u2010lasting effects. The aim of the present study was to investigate the spinal effects of PWT<\/jats:styled-content>2\u2010N<\/jats:styled-content>\/OFQ<\/jats:styled-content> in nociceptive and neuropathic pain models in mice and non\u2010human primates.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Tail withdrawal assay in mice and monkeys was used as a nociceptive pain model and mechanical threshold in mice subjected to chronic constriction injury was used as a neuropathic pain model. The antinociceptive effects of spinally administered N<\/jats:styled-content>\/OFQ<\/jats:styled-content> and PWT2<\/jats:styled-content>\u2010N<\/jats:styled-content>\/OFQ<\/jats:styled-content> were assessed in these models.<\/jats:p><\/jats:sec>Key Results<\/jats:title>PWT2<\/jats:styled-content>\u2010N<\/jats:styled-content>\/OFQ<\/jats:styled-content> mimicked the spinal antinociceptive effects of N<\/jats:styled-content>\/OFQ<\/jats:styled-content> both in nociceptive and neuropathic pain models in mice as well as in non\u2010human primates displaying 40\u2010fold higher potency and a markedly prolonged duration of action. The effects of N<\/jats:styled-content>\/OFQ<\/jats:styled-content> and PWT2<\/jats:styled-content>\u2010N<\/jats:styled-content>\/OFQ<\/jats:styled-content> were sensitive to the N<\/jats:styled-content>\/OFQ<\/jats:styled-content> receptor (NOP<\/jats:styled-content>) antagonist SB<\/jats:styled-content>\u2010612111, but not to opioid receptor antagonists.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>The present study has demonstrated that PWT2<\/jats:styled-content>\u2010N<\/jats:styled-content>\/OFQ<\/jats:styled-content> mimicked the antinociceptive effects of the natural peptide in rodents and non\u2010human primates acting as a potent and longer\u2010lasting NOP<\/jats:styled-content>\u2010selective agonist. More generally, PWT<\/jats:styled-content> derivatives of biologically active peptides can be viewed as innovative pharmacological tools for investigating those conditions and states in which selective and prolonged receptor stimulation promotes beneficial effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13150","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T18:12:15Z","timestamp":1427911935000},"page":"3661-3670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Spinal antinociceptive effects of the novel NOP<\/scp> receptor agonist PWT2<\/scp>\u2010nociceptin\/orphanin FQ<\/scp> in mice and monkeys"],"prefix":"10.1111","volume":"172","author":[{"given":"A","family":"Rizzi","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience University of Ferrara Ferrara 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