{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:13:30Z","timestamp":1781100810766,"version":"3.54.1"},"reference-count":67,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004530","name":"Universiti Putra Malaysia","doi-asserted-by":"publisher","award":["GP-IBT\/2013\/9409600"],"award-info":[{"award-number":["GP-IBT\/2013\/9409600"]}],"id":[{"id":"10.13039\/501100004530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine\/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg\/kg (0.9\u20134.5 mg\/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg\/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine\/nitric oxide\/cGMP pathway and ATP-sensitive K+ channel.<\/jats:p>","DOI":"10.3390\/molecules25225385","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T09:59:47Z","timestamp":1605693587000},"page":"5385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Possible Participation of Ionotropic Glutamate Receptors and l-Arginine-Nitric Oxide-Cyclic Guanosine Monophosphate-ATP-Sensitive K+ Channel Pathway in the Antinociceptive Activity of Cardamonin in Acute Pain Animal Models"],"prefix":"10.3390","volume":"25","author":[{"given":"Chung","family":"Pui Ping","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Nadeem","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Faculty of Industrial Sciences &amp; Technology, University Malaysia Pahang, Gambang 26300, Pahang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daud Ahmad","family":"Israf","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Selangor, Malaysia"},{"name":"Laboratory of Natural Products, Institute of Bioscience, University Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2666-7340","authenticated-orcid":false,"given":"Enoch Kumar","family":"Perimal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Selangor, Malaysia"},{"name":"Australian Research Council Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Roslan","family":"Sulaiman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Selangor, Malaysia"},{"name":"Laboratory of Natural Products, Institute of Bioscience, University Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1055\/s-0028-1097682","article-title":"Cardamonin and alpinetin from the seeds of Amomum subulatum","volume":"29","author":"Rao","year":"1976","journal-title":"Planta Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejphar.2006.03.070","article-title":"Cardamonin, inhibits pro-inflammatory mediators in activated RAW 264.7 cells and whole blood","volume":"538","author":"Ahmad","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.intimp.2012.01.009","article-title":"Cardamonin from Alpinia rafflesiana inhibits inflammatory responses in IFN-\u03b3\/LPS-stimulated BV2 microglia via NF-\u04a1B signalling pathway","volume":"12","author":"Chow","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1097\/00005344-200105000-00011","article-title":"Vasorelaxant effects of cardamonin and alpinetin from Alpinia henryi K. Schum","volume":"37","author":"Wang","year":"2001","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.3390\/molecules19021843","article-title":"Antiproliferative activity and induction of apoptosis in PC-3 cells by the chalcone cardamonin from Campomanesia adamantium (Myrtaceae) in a bioactivity-guided study","volume":"19","author":"Pascoal","year":"2014","journal-title":"Molecules"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.leukres.2011.11.014","article-title":"Cardamonin exerts potent activity against multiple myeloma through blockade of NF-KB pathway in vitro","volume":"36","author":"Qin","year":"2012","journal-title":"Leuk. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.lfs.2014.01.066","article-title":"mTOR inhibition of cardamonin on antiproliferation of A549 cells is involved in a FKBP12 independent fashion","volume":"99","author":"Tang","year":"2012","journal-title":"Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/jbt.21420","article-title":"Cardamonin protects septic mice from acute lung injury by preventing endothelial barrier dysfunction","volume":"26","author":"Wei","year":"2012","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.1021\/jf010016o","article-title":"Structural analysis of a novel antimutagenic compound, 4-hydroxypanduratin A, and the antimutagenic activity of flavonoids in a Thai spice, fingerroot (Boesenbergia pandurata Schult.) against mutagenic heterocyclic amines","volume":"49","author":"Trakoontivakorn","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ejphar.2010.05.024","article-title":"Antiproliferation of cardamonin is involved in mTOR on aortic smooth muscle cells in high fructose-induced insulin resistance rats","volume":"641","author":"Liao","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.bbrc.2009.09.124","article-title":"Cardamonin suppresses melanogenesis by inhibition of Wnt\/\u03b2-catenin signaling","volume":"390","author":"Cho","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pbb.2014.09.011","article-title":"Novel inhibitory effects of cardamonin on thromboxane A2-induced scratching response: Blocking of Gh\/transglutaminase-2 binding to thromboxane A2 receptor","volume":"126","author":"Park","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.taap.2013.10.031","article-title":"Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis","volume":"274","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.abb.2014.05.008","article-title":"The chalcones cardamonin and flavokawain B inhibit the differentiation of preadipocytes to adipocytes by activating ERK","volume":"554","author":"Zhang","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_15","first-page":"341","article-title":"Isolation of Cardamonin and Pinostrobin Chalcone from the Rhizomes of Boesenbergia rotunda (L.) Mansf. and their Cytotoxic Effects on H-29 and MDA-MB-231 Cancer Cell Lines","volume":"9","author":"Mohammed","year":"2019","journal-title":"Nat. Prod. J."},{"key":"ref_16","first-page":"3991","article-title":"Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer","volume":"15","author":"Niu","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1080\/15384101.2019.1673620","article-title":"Cardamonin attenuates chronic inflammation and tumorigenesis in colon","volume":"18","author":"Hou","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.lfs.2012.11.009","article-title":"Novel suppressive effects of cardamonin on the activity and expression of transglutaminase-2 lead to blocking the migration and invasion of cancer cells","volume":"92","author":"Park","year":"2013","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13945","DOI":"10.1038\/s41598-017-14253-8","article-title":"Cardamonin inhibits colonic neoplasia through modulation of MicroRNA expression","volume":"7","author":"James","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1186\/s13046-019-1351-4","article-title":"Cardamonin inhibits breast cancer growth by repressing HIF-1\u03b1-dependent metabolic reprogramming","volume":"38","author":"Jin","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s10637-019-00781-9","article-title":"Cardamonin, a natural chalcone, reduces 5-fluorouracil resistance of gastric cancer cells through targeting Wnt\/\u03b2-catenin signal pathway","volume":"38","author":"Hou","year":"2020","journal-title":"Investig. New Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"BSR20190357","DOI":"10.1042\/BSR20190357","article-title":"Cardamonin exerts anti-gastric cancer activity via inhibiting LncRNA-PVT1-STAT3 axis","volume":"39","author":"Wang","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ejphar.2016.11.009","article-title":"Cardamonin (2\u2032-4\u2032-dihydroxy-6\u2032-methoxychalcone) isolated from Boesenbergia rotunda (L.) Mansf. inhibits CFA-induced rheumatoid arthritis in rats","volume":"794","author":"Voon","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ejphar.2016.12.020","article-title":"Cardamonin attenuates hyperalgesia and allodynia in a mouse model of chronic constriction injury-induced neuropathic pain: Possible involvement of the opioid system","volume":"796","author":"Sambasevam","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1080\/08923973.2017.1418881","article-title":"Cardamonin inhibits pro-inflammatory cytokine production and suppresses NO pathway in PBMCs from patients with primary Sjogren\u2019s syndrome","volume":"40","author":"Benchabane","year":"2018","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.molimm.2006.04.025","article-title":"Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-\u04a1B nuclear translocation and \u04a1-B phosphorylation in RAW 264.7 macrophage cells","volume":"44","author":"Israf","year":"2007","journal-title":"Mol. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.lfs.2011.06.027","article-title":"Cardamonin suppresses nitric oxide production via blocking the IFN-\u03b3\/STAT pathway in endotoxin-challenged peritoneal macrophages of ICR mice","volume":"89","author":"Takahashi","year":"2011","journal-title":"Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.pbb.2013.12.019","article-title":"Novel anti-nociceptive effects of cardamonin via blocking expression of cyclooxygenase-2 and transglutaminase-2","volume":"118","author":"Park","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ping, C.P., Mohamad, T., Shah, T.A., Akhtar, M.N., Perimal, E.K., Akira, A., Ali, I., Ahmad, D., and Sulaiman, M.R. (2018). Antinociceptive effects of cardamonin in mice: Possible involvement of TRPV1, glutamate, and opioid receptors. Molecules, 23.","DOI":"10.3390\/molecules23092237"},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S0028-3908(99)00006-4","article-title":"The role of systemic, spinal and supraspinal l-arginine-nitric oxide-cGMP pathway in thermal hyperalgesia caused by intrathecal injection of glutamate in mice","volume":"38","author":"Ferreira","year":"1999","journal-title":"Neuropharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, S., Zhai, C., Zhang, Y., Yu, Y., Zhang, Y., Ma, L., Li, S., and Qiao, Y. (2016). Cardamonin, a novel antagonist of hTRPA1 cation channel, reveals therapeutic mechanism of pathological pain. Molecules, 21.","DOI":"10.3390\/molecules21091145"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.fitote.2015.07.011","article-title":"Antiallodynic and antihyperalgesic effects of zerumbone on a mouse model of chronic constriction injury-induced neuropathic pain","volume":"105","author":"Zulazmi","year":"2015","journal-title":"Fitoterapia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1744-8069-1-3","article-title":"Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins","volume":"1","author":"Moriyama","year":"2005","journal-title":"Mol. Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.pain.2005.06.001","article-title":"Mechanisms involved in the nociception produced by peripheral protein kinase c activation in mice","volume":"117","author":"Ferreira","year":"2005","journal-title":"Pain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.phrs.2007.04.006","article-title":"Protein kinase C in pain: Involvement of multiple isoforms","volume":"55","author":"Velazquez","year":"2007","journal-title":"Pharmacol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1469-7793.2001.00813.x","article-title":"Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide","volume":"534","author":"Vellani","year":"2001","journal-title":"J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1113\/jphysiol.2006.118620","article-title":"Potentiation of glutamatergic synaptic transmission by protein kinase C-mediated sensitization of TRPV1 at the first sensory synapse","volume":"581","author":"Sikand","year":"2007","journal-title":"J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1744-8069-6-5","article-title":"Regulation of AMPA receptors in spinal nociception","volume":"6","author":"Wang","year":"2010","journal-title":"Mol. Pain"},{"key":"ref_40","unstructured":"Malenka, R. (2009). Glutamate. Intercellular Communication in the Nervous System, Academic Press."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1213\/01.ANE.0000081061.12235.55","article-title":"The role of N-methyl-D-aspartate (NMDA) receptors in pain: A review","volume":"97","author":"Petrenko","year":"2003","journal-title":"Anesth. Analg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1097\/00001756-199603220-00012","article-title":"Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats","volume":"7","author":"Zhou","year":"1996","journal-title":"Neuroreport"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1006\/phrs.1997.0301","article-title":"Tolerance develops to the antinociceptive and motor impairing effects of ACEA-1416, a NMDA receptor antagonist, in the formalin and rotarod tests in mice","volume":"37","author":"Lutfy","year":"1998","journal-title":"Pharmacol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1111\/j.1399-6576.2009.02054.x","article-title":"Nitric oxide and pain:\u2019something old, something new\u2019","volume":"53","author":"Miclescu","year":"2009","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/sj.bjp.0704569","article-title":"NO as a signalling molecule in the nervous system","volume":"135","author":"Esplugues","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/09629350050024348","article-title":"l-NAME causes antinociception by stimulation of the arginine-NO-cGMP pathway","volume":"9","author":"Duarte","year":"2000","journal-title":"Mediat. Inflamm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0197-0186(00)00110-8","article-title":"Antinociceptive effect of spinally injected l-NAME on the acute nociceptive response induced by low concentrations of formalin","volume":"38","author":"Sakurada","year":"2001","journal-title":"Neurochem. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1476-5381.1991.tb12153.x","article-title":"l-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse","volume":"102","author":"Moore","year":"1991","journal-title":"Br. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1097\/00000542-199911000-00035","article-title":"Activation of spinal N-methyl-D-aspartate receptors stimulates a nitric oxide\/cyclic guanosine 3, 5-monophosphate\/glutamate release cascade in nociceptive signaling","volume":"91","author":"Kawamata","year":"1999","journal-title":"Anesthesiology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1744-8069-7-35","article-title":"Activation of ATP-sensitive potassium channels antagonize nociceptive behavior and hyperexcitability of DRG neurons from rats","volume":"7","author":"Du","year":"2011","journal-title":"Mol. Pain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"621","DOI":"10.2174\/1570159X113119990042","article-title":"Potassium channels in peripheral pain pathways: Expression, function and therapeutic potential","volume":"11","author":"Du","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ejphar.2004.07.026","article-title":"Potassium channels and pain: Present realities and future opportunities","volume":"500","author":"Ocana","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0028-3908(00)00097-6","article-title":"Involvement of potassium channels in amitriptyline and clomipramine analgesia","volume":"40","author":"Galeotti","year":"2001","journal-title":"Neuropharmacology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1590\/S1807-59322011000200023","article-title":"Effect of glibenclamide on antinociceptive effects of antidepressants of different classes","volume":"66","author":"Hajhashemi","year":"2011","journal-title":"Clinics"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0014-2999(00)00355-1","article-title":"Activation of ATP-sensitive K+ channels: Mechanism of peripheral antinociceptive action of the nitric oxide donor, sodium nitroprusside","volume":"400","author":"Soares","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00011-006-6109-8","article-title":"Role of NO\/cGMP\/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice","volume":"56","author":"Vale","year":"2007","journal-title":"Inflamm. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.pharep.2014.04.003","article-title":"Nitroxyl inhibits overt pain-like behavior in mice: Role of cGMP\/PKG\/ATP-sensitive potassium channel signaling pathway","volume":"66","author":"Zarpelon","year":"2014","journal-title":"Pharmacol. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1744-8069-5-12","article-title":"Nitric oxide activates ATP-sensitive potassium channels in mammalian sensory neurons: Action by direct S-nitrosylation","volume":"5","author":"Kawano","year":"2009","journal-title":"Mol. Pain"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.fitote.2004.07.002","article-title":"Antinociceptive effect of Melastoma malabathricum ethanolic extract in mice","volume":"75","author":"Sulaiman","year":"2004","journal-title":"Fitoterapia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jep.2011.05.043","article-title":"Antinociceptive effect of the essential oil of Zingiber zerumbet in mice: Possible mechanisms","volume":"137","author":"Khalid","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1124\/jpet.105.092825","article-title":"Analysis of the antinociceptive effect of the flavonoid myricitrin: Evidence for a role of the l-arginine-nitric oxide and protein kinase C pathways","volume":"316","author":"Meotti","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.pbb.2008.09.009","article-title":"The NMDA antagonist MK-801 induces hyperalgesia and increases CSF excitatory amino acids in rats: Reversal by guanosine","volume":"91","author":"Schmidt","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3346\/jkms.2005.20.2.307","article-title":"Antinociceptive interactions between intrathecal gabapentin and MK801 or NBQX in rat formalin test","volume":"20","author":"Yoon","year":"2005","journal-title":"J. Korean Med. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1742-7843.2010.00635.x","article-title":"Zerumbone-induced antinociception: Involvement of the l-arginine-nitric oxide-cGMP-PKC-K+ ATP channel pathways","volume":"108","author":"Perimal","year":"2011","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jep.2013.03.081","article-title":"Evaluation of mechanisms involved in the antinociception of the ethanol extract from the inner bark of Caesalpinia pyramidalis in mice","volume":"148","author":"Santos","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1742-7843.2010.00670.x","article-title":"Possible Participation of Nitric Oxide\/Cyclic Guanosine Monophosphate\/Protein Kinase C\/ATP-Sensitive K+ Channels Pathway in the Systemic Antinociception of Flavokawin B","volume":"108","author":"Mohamad","year":"2011","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1472-8206.2012.01068.x","article-title":"Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice","volume":"28","author":"Rangel","year":"2014","journal-title":"Fundam. Clin. 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