{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:49:28Z","timestamp":1788922168392,"version":"build-2803163510"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"The Deanship of Scientific Research at the Hashemite University, Jordan","award":["34\/2020"],"award-info":[{"award-number":["34\/2020"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-03758-2","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T08:12:33Z","timestamp":1759306353000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antinociceptive effect of Arvelexin in male mouse models"],"prefix":"10.1038","volume":"15","author":[{"given":"Yousra","family":"Bseiso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Gammoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esam","family":"Qnais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna","family":"Oqal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Abudalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badriyah S.","family":"Alotaibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa A. A.","family":"Aljabali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujain F.","family":"Alzaghari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahim","family":"Alqudah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"3758_CR1","doi-asserted-by":"publisher","first-page":"20190275","DOI":"10.1098\/rstb.2019.0275","volume":"374","author":"ET Walters","year":"2019","unstructured":"Walters, E. T., De, C. & Williams, A. C. Evolution of mechanisms and behaviour important for pain. Philos. Trans. R. Soc. B 374, 20190275 (2019).","journal-title":"Philos. Trans. R. Soc. B"},{"key":"3758_CR2","doi-asserted-by":"publisher","first-page":"R129","DOI":"10.1016\/j.cub.2017.01.037","volume":"27","author":"WD Tracey","year":"2017","unstructured":"Tracey, W. D. Nociception. Curr. Biol. 27, R129\u2013R133 (2017).","journal-title":"Curr. Biol."},{"key":"3758_CR3","doi-asserted-by":"publisher","first-page":"662","DOI":"10.3111\/13696998.2010.529379","volume":"13","author":"P Langley","year":"2010","unstructured":"Langley, P. et al. The impact of pain on labor force participation, absenteeism and presenteeism in the European union. J. Med. Econ. 13, 662\u2013672 (2010).","journal-title":"J. Med. Econ."},{"key":"3758_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2013.12.003","author":"Y Wang","year":"2014","unstructured":"Wang, Y. et al. Antinociceptive and anti-inflammatory activities of extract and two isolated flavonoids of Carthamus tinctorius L. J. Ethnopharmacol. https:\/\/doi.org\/10.1016\/j.jep.2013.12.003 (2014).","journal-title":"J. Ethnopharmacol."},{"key":"3758_CR5","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1152\/physiol.00022.2017","volume":"33","author":"LU Sneddon","year":"2018","unstructured":"Sneddon, L. U. Comparative physiology of nociception and pain. Physiology 33, 63\u201373 (2018).","journal-title":"Physiology"},{"key":"3758_CR6","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/35093019","volume":"413","author":"D Julius","year":"2001","unstructured":"Julius, D. & Basbaum, A. I. Molecular mechanisms of nociception. Nature 413, 203\u2013210 (2001).","journal-title":"Nature"},{"key":"3758_CR7","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/j.1742-7843.2011.00804.x","volume":"110","author":"L Ming-Tatt","year":"2012","unstructured":"Ming-Tatt, L. et al. Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice. Basic Clin. Pharmacol. Toxicol. 110, 275\u2013282 (2012).","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"3758_CR8","doi-asserted-by":"publisher","first-page":"284","DOI":"10.3389\/fnmol.2017.00284","volume":"10","author":"JR Deuis","year":"2017","unstructured":"Deuis, J. R., Dvorakova, L. S. & Vetter, I. Methods used to evaluate pain behaviors in rodents. Front. Mol. Neurosci. 10, 284 (2017).","journal-title":"Front. Mol. Neurosci."},{"key":"3758_CR9","first-page":"108","volume":"18","author":"SB Dehkordi","year":"2017","unstructured":"Dehkordi, S. B., Sajedianfard, J. & Owji, A. A. The effect of intra-cerebroventricular injection of insulin on nociception of formalin test in non-diabetic and short-term diabetic rat models. Iran. J. Vet. Res. 18, 108 (2017).","journal-title":"Iran. J. Vet. Res."},{"key":"3758_CR10","doi-asserted-by":"publisher","unstructured":"Numazaki, M. & Tominaga, M. Nociception and TRP channels. Current Drug Targets CNS Neurological Disord. 3 479\u2013485. https:\/\/doi.org\/10.2174\/1568007043336789 (2004).","DOI":"10.2174\/1568007043336789"},{"key":"3758_CR11","doi-asserted-by":"publisher","first-page":"778","DOI":"10.31925\/farmacia.2021.4.20","volume":"69","author":"C Scheau","year":"2021","unstructured":"Scheau, C. et al. Modulation of capsaicin-induced neurogenic vasodilation by acute psychological stress. Farmacia 69, 778\u2013784 (2021).","journal-title":"Farmacia"},{"key":"3758_CR12","doi-asserted-by":"publisher","unstructured":"Neugebauer, V. Metabotropic glutamate receptors-important modulators of nociception and pain behavior. Pain. https:\/\/doi.org\/10.1016\/S0304-3959(02)00140-9 (2002).","DOI":"10.1016\/S0304-3959(02)00140-9"},{"key":"3758_CR13","doi-asserted-by":"publisher","first-page":"e15619","DOI":"10.1016\/j.heliyon.2023.e15619","volume":"9","author":"A Alqudah","year":"2023","unstructured":"Alqudah, A. et al. Lysionotin exerts antinociceptive effects in various models of nociception induction. Heliyon 9, e15619 (2023).","journal-title":"Heliyon"},{"key":"3758_CR14","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1002\/cbdv.201300260","volume":"11","author":"MSC Pedras","year":"2014","unstructured":"Pedras, M. S. C. & Yaya, E. E. Tenualexin other phytoalexins and indole glucosinolates from wild cruciferous species. Chem. Biodivers. 11, 910\u2013918 (2014).","journal-title":"Chem. Biodivers."},{"key":"3758_CR15","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.phytochem.2007.10.019","volume":"69","author":"MSC Pedras","year":"2008","unstructured":"Pedras, M. S. C., Zheng, Q. A., Gadagi, R. S. & Rimmer, S. R. Phytoalexins and polar metabolites from the oilseeds Canola and rapeseed: Differential metabolic responses to the biotroph Albugo Candida and to abiotic stress. Phytochemistry 69, 894\u2013910 (2008).","journal-title":"Phytochemistry"},{"key":"3758_CR16","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/j.1476-5381.2011.01351.x","volume":"164","author":"JS Shin","year":"2011","unstructured":"Shin, J. S. et al. Arvelexin from Brassica rapa suppresses NF-\u03baB-regulated pro-inflammatory gene expression by inhibiting activation of I\u03baB kinase. Br. J. Pharmacol. 164, 145\u2013158 (2011).","journal-title":"Br. J. Pharmacol."},{"key":"3758_CR17","doi-asserted-by":"publisher","first-page":"7398","DOI":"10.1021\/jf3009553","volume":"60","author":"EJ Cho","year":"2012","unstructured":"Cho, E. J. et al. Arvelexin inhibits colonic inflammation by suppression of NF-\u03baB activation in dextran sulfate sodium-induced mice and TNF-\u03b1-induced colonic epithelial cells. J. Agric. Food Chem. 60, 7398\u20137407 (2012).","journal-title":"J. Agric. Food Chem."},{"key":"3758_CR18","doi-asserted-by":"publisher","unstructured":"Animals, N. R. C. (ed) (US) C. for the U. of the G. for the C. and U. of L. Guide for the Care and Use of Laboratory Animals. Guid. Care Use Lab. Anim. https:\/\/doi.org\/10.17226\/12910 (2011).","DOI":"10.17226\/12910"},{"key":"3758_CR19","first-page":"412","volume":"18","author":"R Koster","year":"1959","unstructured":"Koster, R., Anderson, M. & De Beer, E. Acetic acid for analgesic screening. Fed. Proc. 18, 412 (1959).","journal-title":"Fed. Proc."},{"key":"3758_CR20","doi-asserted-by":"publisher","first-page":"110328","DOI":"10.1016\/j.biopha.2020.110328","volume":"129","author":"PH Hung","year":"2020","unstructured":"Hung, P. H. et al. Acetylsalicylic acid-like analgesic effects of trametes versicolor in Wistar rats. Biomed. Pharmacother. 129, 110328 (2020).","journal-title":"Biomed. Pharmacother"},{"key":"3758_CR21","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.3390\/molecules26082297","volume":"26","author":"F Omar","year":"2021","unstructured":"Omar, F. et al. Plant-based Indole alkaloids: A comprehensive overview from a pharmacological perspective. Molecules 26, 2297 (2021).","journal-title":"Molecules"},{"key":"3758_CR22","doi-asserted-by":"publisher","first-page":"688670","DOI":"10.3389\/fphar.2021.688670","volume":"12","author":"H Kushida","year":"2021","unstructured":"Kushida, H., Matsumoto, T., Ikarashi, Y. & Properties Pharmacology, and pharmacokinetics of active Indole and oxindole alkaloids in Uncaria Hook. Front. Pharmacol. 12, 688670 (2021).","journal-title":"Front. Pharmacol."},{"key":"3758_CR23","doi-asserted-by":"publisher","first-page":"e10400","DOI":"10.1016\/j.heliyon.2022.e10400","volume":"8","author":"A Alqudah","year":"2022","unstructured":"Alqudah, A. et al. Ceratonia siliqua leaves ethanol extracts exert anti-nociceptive and anti-inflammatory effects. Heliyon 8, e10400 (2022).","journal-title":"Heliyon"},{"key":"3758_CR24","doi-asserted-by":"crossref","unstructured":"Zhang, Y. et al. Optimization of the purifying process for columbianetin-\u03b2-D-glucopyranoside from angelicae pubescentis radix and evaluation of its analgesic activity using hot plate test. Evidence-Based Complement. Altern. Med. 9944270  (2021).","DOI":"10.1155\/2021\/9944270"},{"key":"3758_CR25","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.neuropharm.2017.04.034","volume":"121","author":"AK Paul","year":"2017","unstructured":"Paul, A. K., Gueven, N. & Dietis, N. Morphine dosing strategy plays a key role in the generation and duration of the produced antinociceptive tolerance. Neuropharmacology 121, 158\u2013166 (2017).","journal-title":"Neuropharmacology"},{"key":"3758_CR26","doi-asserted-by":"publisher","first-page":"229891","DOI":"10.3389\/fphar.2016.00514","volume":"7","author":"G Pang","year":"2016","unstructured":"Pang, G. et al. Blockade of serotonin 5-HT2A receptors suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-treated mice. Front. Pharmacol. 7, 229891 (2016).","journal-title":"Front. Pharmacol."},{"key":"3758_CR27","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.31925\/farmacia.2023.5.20","volume":"71","author":"EY Qnais","year":"2023","unstructured":"Qnais, E. Y. et al. The analgesic properties of the flavonoid Galangin in experimental animal models of nociception. Farmacia 71, 1054\u20131063 (2023).","journal-title":"Farmacia"},{"key":"3758_CR28","doi-asserted-by":"publisher","first-page":"509","DOI":"10.3897\/pharmacia.70.e104828","volume":"70","author":"Y Bseiso","year":"2023","unstructured":"Bseiso, Y. et al. 2\u02b9,3,3,5\u02b9-Tetramethyl-4\u02b9-nitro-2\u02b9H-1,3\u02b9-bipyrazole exerts antinociceptive effect using various nociception models. Pharmacia 70, 509\u2013517 (2023).","journal-title":"Pharmacia"},{"key":"3758_CR29","first-page":"2068","volume":"28","author":"Q Jarrar","year":"2024","unstructured":"Jarrar, Q. et al. Unveiling the antinociceptive mechanisms of methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate: Insights from nociceptive assays in mice. Eur. Rev. Med. Pharmacol. Sci. 28, 2068\u20132083 (2024).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"3758_CR30","doi-asserted-by":"publisher","first-page":"615","DOI":"10.56499\/jppres23.1878_12.4.615","volume":"12","author":"MH Al-Bzour","year":"2024","unstructured":"Al-Bzour, M. H. et al. Exploring the antinociceptive potential of homoeriodictyol in nociception models. J. Pharm. Pharmacogn. Res. 12, 615\u2013623 (2024).","journal-title":"J. Pharm. Pharmacogn. Res."},{"key":"3758_CR31","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/S0304-3959(00)00362-6","volume":"89","author":"J Du","year":"2001","unstructured":"Du, J., Koltzenburg, M. & Carlton, S. M. Glutamate-induced excitation and sensitization of nociceptors in rat glabrous skin. Pain 89, 187\u2013198 (2001).","journal-title":"Pain"},{"key":"3758_CR32","doi-asserted-by":"publisher","first-page":"e14185","DOI":"10.1016\/j.heliyon.2023.e14185","volume":"9","author":"OS Gammoh","year":"2023","unstructured":"Gammoh, O. S., Qnais, E., Bseiso, Y., Alrosan, K. & Alqudah, A. Evaluation of the antinociceptive effect of Valerian and hops combination in experimental animal models: Involvement of the opioid system. Heliyon 9, e14185 (2023).","journal-title":"Heliyon"},{"key":"3758_CR33","unstructured":"Elisa Kits online. Cited in more than 3600 Publications-Cusabio. https:\/\/www.cusabio.com\/catalog-11-1.html"},{"key":"3758_CR34","doi-asserted-by":"publisher","unstructured":"Tj\u00f8lsen, A., Berge, O. G., Hunskaar, S., Rosland, J. H. & Hole, K. The formalin test: An evaluation of the method. Pain. https:\/\/doi.org\/10.1016\/0304-3959(92)90003-T (1992).","DOI":"10.1016\/0304-3959(92)90003-T"},{"key":"3758_CR35","doi-asserted-by":"crossref","unstructured":"Lopes, D. M., Cater, H. L., Thakur, M., Wells, S. & McMahon, S. B. A refinement to the formalin test in mice. F1000Research 8, 891 (2019).","DOI":"10.12688\/f1000research.18338.1"},{"key":"3758_CR36","doi-asserted-by":"publisher","first-page":"e80650","DOI":"10.1371\/journal.pone.0080650","volume":"8","author":"M Aghajani","year":"2013","unstructured":"Aghajani, M. et al. Effects of dominant\/subordinate social status on formalin-induced pain and changes in serum proinflammatory cytokine concentrations in mice. PLoS One 8, e80650 (2013).","journal-title":"PLoS One"},{"key":"3758_CR37","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S0014-2999(99)00790-6","volume":"387","author":"RA Ribeiro","year":"2000","unstructured":"Ribeiro, R. A. et al. Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice. Eur. J. Pharmacol. 387, 111\u2013118 (2000).","journal-title":"Eur. J. Pharmacol."},{"key":"3758_CR38","doi-asserted-by":"publisher","unstructured":"Le Bars, D., Gozariu, M. & Cadden, S. W. Animal models of nociception. Pharmacol. Rev. https:\/\/doi.org\/10.1002\/9783527611942.ch9 (2001).","DOI":"10.1002\/9783527611942.ch9"},{"key":"3758_CR39","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","volume":"31","author":"E Ricciotti","year":"2011","unstructured":"Ricciotti, E. & Fitzgerald, G. A. Prostaglandins and inflammation. Arterioscler. Thromb. Vasc Biol. 31, 986\u20131000 (2011).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"3758_CR40","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1007\/s00011-007-6088-4","volume":"56","author":"A Koch","year":"2007","unstructured":"Koch, A. et al. Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients. Inflamm. Res. 56, 32\u201337 (2007).","journal-title":"Inflamm. Res."},{"key":"3758_CR41","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1590\/S0100-879X2005000300016","volume":"38","author":"TR Lavich","year":"2005","unstructured":"Lavich, T. R., Cordeiro, R. S. B., Silva, P. M. R. & Martins, M. A. A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics. Braz. J. Med. Biol. Res. 38, 445\u2013451 (2005).","journal-title":"Braz. J. Med. Biol. Res."},{"key":"3758_CR42","doi-asserted-by":"crossref","unstructured":"Abdul Rahim, M. H. et al. Methanolic extract of clinacanthus nutans exerts antinociceptive activity via the opioid\/nitric oxide-mediated, but cGMP-independent, pathways. Evidence-based complement. Altern. Med. (2016).","DOI":"10.1155\/2016\/1494981"},{"issue":"3","key":"3758_CR43","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.3390\/ph3051335","volume":"3","author":"H Vanegas","year":"2010","unstructured":"Vanegas, H., Vazquez, E. & Tortorici, V. NSAIDs opioids, cannabinoids and the control of pain by the central nervous system. Pharmaceuticals 3(3), 1335\u20131347 (2010).","journal-title":"Pharmaceuticals"},{"key":"3758_CR44","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.3390\/ijms19082164","volume":"19","author":"MF Yam","year":"2018","unstructured":"Yam, M. F. et al. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int. J. Mol. Sci. 19, 2164 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"3758_CR45","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.13005\/bpj\/1216","volume":"10","author":"E Qnais","year":"2017","unstructured":"Qnais, E., Bseiso, Y., Wedyan, M. & Alkhateeb, H. Evaluation of analgesic activity of the methanol extract from the leaves of Arum palaestinum in mice and rats. Biomed. Pharmacol. J. 10, 1159\u20131166 (2017).","journal-title":"Biomed. Pharmacol. J."},{"key":"3758_CR46","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.nut.2019.04.007","volume":"66","author":"G Bj\u00f8rklund","year":"2019","unstructured":"Bj\u00f8rklund, G. et al. Does diet play a role in reducing nociception related to inflammation and chronic pain? Nutrition 66, 153\u2013165 (2019).","journal-title":"Nutrition"},{"key":"3758_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneumeth.2014.04.017","volume":"232","author":"MVP De Sousa","year":"2014","unstructured":"De Sousa, M. V. P., Ferraresi, C., De Magalh\u00e3es, A. C., Yoshimura, E. M. & Hamblin, M. R. Building, testing and validating a set of home-made von Frey filaments: A precise, accurate and cost effective alternative for nociception assessment. J. Neurosci. Methods. 232, 1\u20135 (2014).","journal-title":"J. Neurosci. Methods"},{"key":"3758_CR48","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jneumeth.2013.06.005","volume":"219","author":"RK Banik","year":"2013","unstructured":"Banik, R. K. & Kabadi, R. A. A modified hargreaves\u2019 method for assessing threshold temperatures for heat nociception. J. Neurosci. Methods 219, 41\u201351 (2013).","journal-title":"J. Neurosci. Methods"},{"key":"3758_CR49","doi-asserted-by":"publisher","first-page":"19506","DOI":"10.1021\/acsomega.0c01775","volume":"5","author":"AL Gomes J\u00fanior","year":"2020","unstructured":"Gomes J\u00fanior, A. L. et al. Anti-inflammatory, antinociceptive, and antioxidant properties of anacardic acid in experimental models. ACS Omega 5, 19506\u201319515 (2020).","journal-title":"ACS Omega"},{"key":"3758_CR50","doi-asserted-by":"publisher","first-page":"218","DOI":"10.3344\/kjp.23355","volume":"37","author":"P Yaghooti","year":"2024","unstructured":"Yaghooti, P. & Alimoahmmadi, S. Assessment of antinociceptive property of Cynara scolymus L. and possible mechanism of action in the formalin and writhing models of nociception in mice. Korean J. Pain 37, 218\u2013232 (2024).","journal-title":"Korean J. Pain"},{"key":"3758_CR51","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/S0306-4522(00)00574-1","volume":"103","author":"S Sweitzer","year":"2001","unstructured":"Sweitzer, S., Martin, D. & DeLeo, J. A. Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain. Neuroscience 103, 529\u2013539 (2001).","journal-title":"Neuroscience"},{"key":"3758_CR52","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.npep.2004.12.017","volume":"39","author":"Z Wiesenfeld-Hallin","year":"2005","unstructured":"Wiesenfeld-Hallin, Z., Xu, X. J., Crawley, J. N. & H\u00f6kfelt, T. Galanin and spinal nociceptive mechanisms: Recent results from transgenic and knock-out models. Neuropeptides 39, 207\u2013210 (2005).","journal-title":"Neuropeptides"},{"key":"3758_CR53","doi-asserted-by":"publisher","first-page":"109202","DOI":"10.1016\/j.neuropharm.2022.109202","volume":"217","author":"D Jin","year":"2022","unstructured":"Jin, D., Chen, H., Huang, Y., Chen, S. R. & Pan, H. L. \u03b4-Opioid receptors in primary sensory neurons tonically restrain nociceptive input in chronic pain but do not enhance morphine analgesic tolerance. Neuropharmacology 217, 109202 (2022).","journal-title":"Neuropharmacology"},{"key":"3758_CR54","doi-asserted-by":"publisher","first-page":"17165","DOI":"10.1074\/jbc.M313328200","volume":"279","author":"E Phillips","year":"2004","unstructured":"Phillips, E., Reeve, A., Bevan, S. & McIntyre, P. Identification of species-specific determinants of the action of the antagonist Capsazepine and the agonist PPAHV on TRPV1. J. Biol. Chem. 279, 17165\u201317172 (2004).","journal-title":"J. Biol. Chem."},{"key":"3758_CR55","doi-asserted-by":"publisher","first-page":"424363","DOI":"10.3389\/fnmol.2018.00464","volume":"11","author":"V Pereira","year":"2019","unstructured":"Pereira, V. & Goudet, C. Emerging trends in pain modulation by metabotropic glutamate receptors. Front. Mol. Neurosci. 11, 424363 (2019).","journal-title":"Front. Mol. Neurosci."},{"key":"3758_CR56","doi-asserted-by":"crossref","unstructured":"Raju, K. et al. Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation. Sci. Signal 8 (2015).","DOI":"10.1126\/scisignal.aaa4312"},{"key":"3758_CR57","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/AIA.0b013e318034194e","volume":"45","author":"JM Zhang","year":"2007","unstructured":"Zhang, J. M., An, J. & Cytokines Inflammation and pain. Int. Anesthesiol. Clin. 45, 27 (2007).","journal-title":"Int. Anesthesiol. Clin."},{"key":"3758_CR58","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.cbi.2014.10.004","volume":"224","author":"JS Shin","year":"2014","unstructured":"Shin, J. S. et al. Anti-inflammatory effects of 7-hydroxyl-1-methylindole-3-acetonitrile, a synthetic arvelexin derivative, on the macrophages through destabilizing mPGES-1 mRNA and suppressing NF-\u03baB activation. Chem. Biol. Interact. 224, 68\u201377 (2014).","journal-title":"Chem. Biol. Interact."},{"key":"3758_CR59","doi-asserted-by":"crossref","unstructured":"Mogil, J. S. Sex differences in pain and pain inhibition: Multiple explanations of a controversial phenomenon. Nat. Rev. Neurosci. 13, 859\u2013866 (2012).","DOI":"10.1038\/nrn3360"},{"key":"3758_CR60","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.lfs.2012.06.009","volume":"92","author":"RM Craft","year":"2013","unstructured":"Craft, R. M., Marusich, J. A. & Wiley, J. L. Sex differences in cannabinoid pharmacology: A reflection of differences in the endocannabinoid system? Life Sci. 92, 476\u2013481 (2013).","journal-title":"Life Sci."},{"key":"3758_CR61","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1037\/a0012931","volume":"16","author":"RM Craft","year":"2008","unstructured":"Craft, R. M. Sex differences in analgesic, reinforcing, discriminative, and motoric effects of opioids. Exp. Clin. Psychopharmacol. 16, 376\u2013385 (2008).","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"3758_CR62","doi-asserted-by":"publisher","first-page":"S26","DOI":"10.1016\/j.pain.2007.10.014","volume":"132","author":"JD Greenspan","year":"2007","unstructured":"Greenspan, J. D. et al. Studying sex and gender differences in pain and analgesia: A consensus report. Pain 132, S26\u2013S45 (2007).","journal-title":"Pain"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-03758-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-03758-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-03758-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:08:54Z","timestamp":1759309734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-03758-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3758"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-03758-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]},"assertion":[{"value":"14 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The ethical conduct of the experiments with live animals was in strict compliance with the ethical guidelines set by the Hashemite University (IRB number: 20\/2\/2018\/2019), adhering to the principles of the U.S. National Institutes of Health and the ARRIVE guidelines on the humane use and care of laboratory animals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statements"}}],"article-number":"34127"}}