{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:53:29Z","timestamp":1790189609677,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T00:00:00Z","timestamp":1509580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as \u201ccip\u00f3-una\u201d, it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10\u2013100 mg\/kg) in male Swiss mice. We also investigated the involvement of TRPV1 (transient receptor potential vanilloid 1), TRPA1 (transient receptor potential ankyrin 1), TRPM8 (transient receptor potential melastatin 8), and ASIC (acid-sensing ion channel), as well as the opioidergic, glutamatergic, and supraspinal pathways. Moreover, the nociceptive response was reduced (30 mg\/kg) in the early and late phase of the formalin test. DEAB activity appears to involve the opioid system, TRPM8, and ASIC receptors, clearly showing that the DEAB alleviates acute pain in mice and suggesting the involvement of the TRPM8 and ASIC receptors and the opioid system in acute pain relief.<\/jats:p>","DOI":"10.3390\/ijms18112304","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T04:43:13Z","timestamp":1509684193000},"page":"2304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Involvement of Opioid System, TRPM8, and ASIC Receptors in Antinociceptive Effect of Arrabidaea brachypoda (DC) Bureau"],"prefix":"10.3390","volume":"18","author":[{"given":"Vin\u00edcius","family":"Rodrigues","sequence":"first","affiliation":[{"name":"S\u00e3o Paulo State University (UNESP), Biosciences Institute, Department of Physiology, Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3578-1869","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Rocha","sequence":"additional","affiliation":[{"name":"Federal University of Maranh\u00e3o, Department of Chemistry, Av. dos Portugueses, 1966\u2014Bacanga, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"P\u00e9rico","sequence":"additional","affiliation":[{"name":"S\u00e3o Paulo State University (UNESP), Biosciences Institute, Department of Physiology, Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Santos","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Gastroenterology Unit (USF), Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Ohara","sequence":"additional","affiliation":[{"name":"S\u00e3o Paulo State University (UNESP), Biosciences Institute, Department of Physiology, Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarine","family":"Nishijima","sequence":"additional","affiliation":[{"name":"S\u00e3o Paulo State University (UNESP), Biosciences Institute, Department of Physiology, Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerson","family":"Ferreira Queiroz","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU\u2013Rue Michel-Servet 1, CH-1211 Geneva 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-952X","authenticated-orcid":false,"given":"Jean-Luc","family":"Wolfender","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU\u2013Rue Michel-Servet 1, CH-1211 Geneva 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00facia","family":"Rocha","sequence":"additional","affiliation":[{"name":"S\u00e3o Paulo State University (UNESP), Biosciences Institute, Department of Physiology, Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adair","family":"Santos","sequence":"additional","affiliation":[{"name":"Federal University of Santa Catarina, Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Trindade, Florianopolis 88040-900, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagner","family":"Vilegas","sequence":"additional","affiliation":[{"name":"S\u00e3o Paulo State University (UNESP), Biosciences Institute, S\u00e3o Vicente 11330-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-3777","authenticated-orcid":false,"given":"Cl\u00e9lia","family":"Hiruma-Lima","sequence":"additional","affiliation":[{"name":"S\u00e3o Paulo State University (UNESP), Biosciences Institute, Department of Physiology, Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mam.2005.07.008","article-title":"Medicinal plants: Traditions of yesterday and drugs of tomorrow","volume":"27","year":"2006","journal-title":"Mol. Asp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rishton, G.M. (2008). Natural Products as a Robust Source of New Drugs and Drug Leads: Past Successes and Present Day Issues. Am. J. Cardiol., 101.","DOI":"10.1016\/j.amjcard.2008.02.007"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s11101-013-9315-3","article-title":"Ecological phytochemistry of Cerrado (Brazilian savanna) plants","volume":"12","author":"Novaes","year":"2013","journal-title":"Phytochem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rodrigues, E., Mendes, F.R., and Negri, G. (2006). Plants indicated by Brazilian Indians to central nervous system disturbances: A bibliographical approach. Curr. Med. Chem., 211\u2013244.","DOI":"10.2174\/187152406778226725"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.jep.2010.10.009","article-title":"Anti-inflammatory and antinociceptive effects of Arrabidaea brachypoda (DC.) Bureau roots","volume":"133","author":"Vilela","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.phytochem.2016.12.002","article-title":"Gastroprotective effects of hydroethanolic root extract of Arrabidaea brachypoda: Evidences of cytoprotection and isolation of unusual glycosylated polyphenols","volume":"135","author":"Marcourt","year":"2017","journal-title":"Phytochemistry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1021\/np401060j","article-title":"Dimeric Flavonoids from Arrabidaea brachypoda and Assessment of Their Anti-Trypanosoma cruzi Activity","volume":"77","author":"Queiroz","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0031-6997(24)01514-X","article-title":"Animal models of nociception","volume":"53","author":"Gozariu","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neuroscience.2011.12.041","article-title":"Tests and models of nociception and pain in rodents","volume":"211","author":"Barrot","year":"2012","journal-title":"Neuroscience"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0304-3959(92)90003-T","article-title":"The formalin test: An evaluation of the method","volume":"51","author":"Berge","year":"1992","journal-title":"Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0304-3959(87)90088-1","article-title":"The formalin test in mice: Dissociation between inflammatory and non-inflammatory pain","volume":"30","author":"Hunskaar","year":"1987","journal-title":"Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1111\/j.1460-9568.1994.tb00323.x","article-title":"Intracellular Messengers Contributing to Persistent Nociception and Hyperalgesia Induced by L-glutamate and Substance P in the Rat Formalin Pain Model","volume":"6","author":"Coderre","year":"1994","journal-title":"Eur. J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13525","DOI":"10.1073\/pnas.0705924104","article-title":"TRPA1 mediates formalin-induced pain","volume":"104","author":"McNamara","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13519","DOI":"10.1073\/pnas.0705923104","article-title":"4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1","volume":"104","author":"Trevisani","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jpain.2010.06.011","article-title":"The influence of non-nociceptive factors on hot-plate latency in rats","volume":"12","author":"Gunn","year":"2011","journal-title":"J. Pain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2174\/1568007043336789","article-title":"Nociception and TRP Channels","volume":"3","author":"Numazaki","year":"2004","journal-title":"Curr. Drug Targets CNS Neurol. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/gb-2011-12-3-218","article-title":"The transient receptor potential family of ion channels","volume":"12","author":"Nilius","year":"2011","journal-title":"Genome Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00281-015-0526-0","article-title":"TRPs and pain","volume":"38","author":"Dai","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"ref_19","first-page":"171","article-title":"ThermoTRPs and Pain","volume":"22","author":"Laing","year":"2016","journal-title":"Neuroscience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.brainresrev.2008.12.018","article-title":"Roles of transient receptor potential channels in pain","volume":"60","author":"Stucky","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuropharm.2015.02.009","article-title":"Acid-Sensing Ion Channels and nociception in the peripheral and central nervous systems","volume":"94","author":"Deval","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nrn3529","article-title":"Acid-sensing ion channels in pain and disease","volume":"14","author":"Wemmie","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nature01905","article-title":"Proton-sensing G-protein-coupled receptors","volume":"425","author":"Ludwig","year":"2003","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1177\/0022034515618382","article-title":"Roles of Proton-Sensing Receptors in the Transition from Acute to Chronic Pain","volume":"95","author":"Sun","year":"2016","journal-title":"J. Dent. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41415","DOI":"10.1038\/srep41415","article-title":"TDAG8 involved in initiating inflammatory hyperalgesia and establishing hyperalgesic priming in mice","volume":"7","author":"Dai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Huang, W.-Y., Dai, S.-P., Chang, Y.-C., and Sun, W.-H. (2015). Acidosis Mediates the Switching of Gs-PKA and Gi-PKC\u03b5 Dependence in Prolonged Hyperalgesia Induced by Inflammation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125022"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chen, Y.-J., Huang, C.-W., Lin, C.-S., Chang, W.-H., and Sun, W.-H. (2009). Expression and Function of Proton-Sensing G-Protein-Coupled Receptors in Inflammatory Pain. Mol. Pain, 5.","DOI":"10.1186\/1744-8069-5-39"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1016\/j.pain.2013.06.043","article-title":"TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain","volume":"154","author":"Liu","year":"2013","journal-title":"Pain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1523\/JNEUROSCI.4846-06.2007","article-title":"Modulation of the Cold-Activated Channel TRPM8 by Lysophospholipids and Polyunsaturated Fatty Acids","volume":"27","author":"Andersson","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1097\/ALN.0b013e318238bba6","article-title":"Molecular Mechanisms of Opioid Receptor-Dependent Signalling and Behaviour","volume":"115","author":"Bruchas","year":"2011","journal-title":"Anesthesiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1476-5381.1980.tb07041.x","article-title":"A classification of opiate receptors that mediate antinociception in animals","volume":"69","author":"Tyers","year":"1980","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0024-3205(99)00417-8","article-title":"Potent antinociceptive effects of TRK-820, a novel \u03ba-opioid receptor agonist","volume":"65","author":"Endoh","year":"1999","journal-title":"Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/jps.3030460322","article-title":"A note on a simple apparatus for detecting neurological deficit in rats and mice","volume":"46","author":"Dunham","year":"1957","journal-title":"J. Am. Pharm. Assoc. Am. Pharm. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0022-3565(25)05180-8","article-title":"Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines","volume":"107","author":"Eddy","year":"1953","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.ijbiomac.2011.10.023","article-title":"Antinociception of \u03b2-d-glucan from Pleurotus pulmonarius is possibly related to protein kinase C inhibition","volume":"50","author":"Baggio","year":"2012","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/0028-3908(92)90057-V","article-title":"The capsaicin test in mice for evaluating tachykinin antagonists in the spinal cord","volume":"31","author":"Sakurada","year":"1992","journal-title":"Neuropharmacology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0006-8993(01)03240-1","article-title":"Mechanisms underlying the nociception and paw oedema caused by injection of glutamate into the mouse paw","volume":"924","author":"Beirith","year":"2002","journal-title":"Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0022-3565(24)38152-2","article-title":"Antinociceptive properties of the new alkaloid, cis-8, 10-di-N-propyllobelidiol hydrochloride dihydrate isolated from Siphocampylus verticillatus: Evidence for the mechanism of action","volume":"289","author":"Santos","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.neuropharm.2005.01.012","article-title":"Mechanisms involved in the antinociception caused by agmatine in mice","volume":"48","author":"Santos","year":"2005","journal-title":"Neuropharmacology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:49:11Z","timestamp":1760208551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,2]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11]]}},"alternative-id":["ijms18112304"],"URL":"https:\/\/doi.org\/10.3390\/ijms18112304","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,2]]}}}