{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:08:14Z","timestamp":1791065294622,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1044414"],"award-info":[{"award-number":["APP1044414"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1063798"],"award-info":[{"award-number":["APP1063798"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1067940"],"award-info":[{"award-number":["APP1067940"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Acid\u2010sensing ion channels (ASICs) are primary acid sensors in mammals, with the ASIC1b and ASIC3 subtypes being involved in peripheral nociception. The antiprotozoal drug diminazene is a moderately potent ASIC inhibitor, but its analgesic activity has not been assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We determined the ASIC subtype selectivity of diminazene and the mechanism by which it inhibits ASICs using voltage\u2010clamp electrophysiology of <jats:italic>Xenopus<\/jats:italic> oocytes expressing ASICs 1\u20133. Its peripheral analgesic activity was then assessed relative to APETx2, an ASIC3 inhibitor, and morphine, in a Freund's complete adjuvant (FCA)\u2010induced rat model of inflammatory pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Diminazene inhibited homomeric rat ASICs with IC<jats:sub>50<\/jats:sub> values of ~200\u2013800\u00a0nM, <jats:italic>via<\/jats:italic> an open channel and subtype\u2010dependent mechanism. In rats with FCA\u2010induced inflammatory pain in one hindpaw, diminazene and APETx2 evoked more potent peripheral antihyperalgesia than morphine, but the effect was partial for APETx2. APETx2 potentiated rat ASIC1b at concentrations 30\u2010fold to 100\u2010fold higher than the concentration inhibiting ASIC3, which may have implications for its use in <jats:italic>in vivo<\/jats:italic> experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Diminazene and APETx2 are moderately potent ASIC inhibitors, both inducing peripheral antihyperalgesia in a rat model of chronic inflammatory pain. APETx2 has a more complex ASIC pharmacology, which must be considered when it is used as a supposedly selective ASIC3 inhibitor <jats:italic>in vivo<\/jats:italic>. Our use of outbred rats revealed responders and non\u2010responders when ASIC inhibition was used to alleviate inflammatory pain, which is aligned with the concept of number\u2010needed\u2010to\u2010treat in human clinical studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.12\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.12\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14089","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T07:06:37Z","timestamp":1510643197000},"page":"2204-2218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Inhibition of acid\u2010sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain"],"prefix":"10.1111","volume":"175","author":[{"given":"Jia Yu Peppermint","family":"Lee","sequence":"first","affiliation":[{"name":"UQ Centre for Clinical Research, Faculty of Medicine The University of Queensland  St Lucia QLD 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