{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:09:39Z","timestamp":1772928579535,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2013,4,10]],"date-time":"2013-04-10T00:00:00Z","timestamp":1365552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Stephanolepis hispidus is one of the most common filefish species in Brazil. Its skin is traditionally used as a complementary treatment for inflammatory disorders. However, there are very few studies on chemical and pharmacological properties using the skin of this fish. This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin (SAE) in different nociception models. Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice. In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 (PGE2) in mice. This potent antinociceptive effect was observed in the hot plate model too, but not in tail-flick test. Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models. In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells. Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system. Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain.<\/jats:p>","DOI":"10.3390\/md11041221","type":"journal-article","created":{"date-parts":[[2013,4,10]],"date-time":"2013-04-10T11:52:27Z","timestamp":1365594747000},"page":"1221-1234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation"],"prefix":"10.3390","volume":"11","author":[{"given":"Vinicius","family":"Carvalho","sequence":"first","affiliation":[{"name":"Laboratory of Inflammation, IOC, Fiocruz, Rio de Janeiro-RJ, 21045-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lohengrin","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Division of Marine Ecosystems, Department of Oceanography, IEAPM, Arraial do Cabo-RJ, 28930-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taline","family":"Conde","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, INCQS, Fiocruz, Rio de Janeiro-RJ, 21045-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Zamith","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, INCQS, Fiocruz, Rio de Janeiro-RJ, 21045-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, INCQS, Fiocruz, Rio de Janeiro-RJ, 21045-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Surrage","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, IOC, Fiocruz, Rio de Janeiro-RJ, 21045-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valber","family":"Frutuoso","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, IOC, Fiocruz, Rio de Janeiro-RJ, 21045-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"Castro-Faria-Neto","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, IOC, Fiocruz, Rio de Janeiro-RJ, 21045-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Amendoeira","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, INCQS, Fiocruz, Rio de Janeiro-RJ, 21045-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.3390\/md7040689","article-title":"The antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa","volume":"7","author":"Mella","year":"2009","journal-title":"Mar. Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.3390\/md9102075","article-title":"Vasorelaxation, induced by Dictyota pulchella (Dictyotaceae), a brown alga, is mediated via inhibition of calcium influx in rats","volume":"9","author":"Queiroz","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3390\/md203123","article-title":"Biomedical compounds from marine organisms","volume":"2","author":"Jha","year":"2004","journal-title":"Mar. Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1517\/13543776.9.9.1207","article-title":"Marine natural products as therapeutic agents","volume":"9","author":"Kerr","year":"1999","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.3390\/md7040787","article-title":"Towards commercial production of sponge medicines","volume":"7","author":"Koopmans","year":"2009","journal-title":"Mar. Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.tips.2010.02.005","article-title":"The odyssey of marine pharmaceuticals: A current pipeline perspective","volume":"31","author":"Mayer","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.3390\/md8072038","article-title":"Prebiotics from marine macroalgae for human and animal health applications","volume":"8","author":"Murphy","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_8","unstructured":"Nelson, J.S. (2006). Fishes of the World, John Wiley & Sons. [4th]."},{"key":"ref_9","unstructured":"Scott, W.B., and Scott, M.G. (1988). Atlantic Fishes of Canada, Canadian Bulletin of Fisheries and Aquatic Sciences. [1st]."},{"key":"ref_10","unstructured":"Figueiredo, J.L. (2002). Peixes da Zona Econ\u00f4mica Exclusiva da Regi\u00e3o Sudeste-Sul do Brasil: Levantamento Com Rede de Meia \u00c1gua, da Universidade de S\u00e3o Paulo. [1st]."},{"key":"ref_11","first-page":"1061","article-title":"Monacanthidae","volume":"Volume 2","author":"Post","year":"1990","journal-title":"Clofeta: Check-List of the Fishes of the Eastern Tropical Atlantic"},{"key":"ref_12","unstructured":"Szpilman, M. (2000). Peixes Marinhos do Brasil: Guia Pr\u00e1tico de Identifica\u00e7\u00e3o, LTDA. [1st]."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pieroni, A., and Price, L.L. (2006). Eating and Healing: Traditional Food as Medicine, Haworth Press. [1st].","DOI":"10.1201\/9781482293616"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0378-8741(03)00225-3","article-title":"Fish Balistes capriscus skin extract-induced relaxation in mesenteric arterial bed of rat","volume":"88","author":"Cavalli","year":"2003","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Muccilo-Baisch, A.L., Silva, D.B., Andrade, A., Carrazzoni, D., Vaz, M.R.C., Furlong, E.B., and Soares, M.C.F. (2007). Effects of aqueous extract from Stephanolepis hispidus on blood pressure in the normal and in l-NAME-induced hypertensive rats. Online Braz. J. Nurs., 6.","DOI":"10.17665\/1676-4285.2007836"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.pharmthera.2011.10.008","article-title":"TRPA1 antagonists as potential analgesic drugs","volume":"133","author":"Andrade","year":"2011","journal-title":"Pharmacol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1089\/jmf.2009.0099","article-title":"Antinociceptive activity of aqueous extract of Bowdichia virgilioides in mice","volume":"13","author":"Silva","year":"2010","journal-title":"J. Med. Food"},{"key":"ref_18","first-page":"907","article-title":"Pemedolac: A novel and long-acting non-narcotic analgesic","volume":"248","author":"Chau","year":"1989","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0304-3959(82)90014-8","article-title":"Plasma morphine concentrations during chronic oral administration in patients with cancer pain","volume":"13","author":"Neumann","year":"1982","journal-title":"Pain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1089\/jir.1985.5.403","article-title":"Pharmacokinetics of recombinant leukocyte A interferon following various routes and modes of administration to the dog","volume":"5","author":"Gibson","year":"1985","journal-title":"J. Interferon Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00424-010-0784-6","article-title":"Understanding inflammatory pain: Ion channels contributing to acute and chronic nociception","volume":"459","author":"Linley","year":"2010","journal-title":"Pflugers Arch."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00003495-199700532-00004","article-title":"The complexity of physiopharmacologic aspects of pain","volume":"53","author":"Besson","year":"1997","journal-title":"Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0014-2999(99)00790-6","article-title":"Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice","volume":"387","author":"Ribeiro","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1248\/bpb.34.1170","article-title":"Prostaglandin E2 and pain\u2014An update","volume":"34","author":"Kawabata","year":"2011","journal-title":"Biol. Pharm. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.jep.2011.08.032","article-title":"Anti-Inflammatory and antinociceptive effects of the stem bark of byrsonima intermedia A","volume":"137","author":"Orlandi","year":"2011","journal-title":"Juss. J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/1056-8719(94)00077-H","article-title":"Hot plate versus tail flick: Evaluation of acute tolerance to continuous morphine infusion in the rat model","volume":"34","author":"Langerman","year":"1995","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4238\/vol8-2gmr588","article-title":"Genotoxicity testing of Ambelania occidentalis (Apocynaceae) leaf extract in vivo","volume":"8","author":"Castro","year":"2009","journal-title":"Genet. Mol. Res."},{"key":"ref_28","first-page":"412","article-title":"Acetic acid for analgesic screening","volume":"18","author":"Koster","year":"1959","journal-title":"Fed. Proc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.phymed.2003.09.002","article-title":"Antinociceptive effect of Nidularium procerum: A Bromeliaceae from the Brazilian coastal rain forest","volume":"12","author":"Amendoeira","year":"2005","journal-title":"Phytomedicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1590\/S0100-879X2005000300016","article-title":"A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics","volume":"38","author":"Lavich","year":"2005","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_31","first-page":"74","article-title":"A method for determining loss of pain sensation","volume":"72","author":"Smith","year":"1941","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0378-4274(96)03847-7","article-title":"The contribution of cytotoxicity to DNA-effects in the single cell gel test (comet assay)","volume":"90","author":"Hartmann","year":"1997","journal-title":"Toxicol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1385\/1-59259-973-7:275","article-title":"The comet assay: A sensitive genotoxicity test for the detection of DNA damage and repair","volume":"314","author":"Speit","year":"2006","journal-title":"Methods Mol. Biol."},{"key":"ref_34","first-page":"103","article-title":"A comparison between manual microscopic analysis and computerized image analysis in the single cell gel electrophoresis assay","volume":"3","author":"Kobayashi","year":"1995","journal-title":"MMS Commun."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/11\/4\/1221\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:46:03Z","timestamp":1760219163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/11\/4\/1221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,10]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2013,4]]}},"alternative-id":["md11041221"],"URL":"https:\/\/doi.org\/10.3390\/md11041221","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,10]]}}}