{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:26:28Z","timestamp":1761719188283,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chung-Ang University Research Grants in 2021","award":["NRF-2020R1C1C1011263"],"award-info":[{"award-number":["NRF-2020R1C1C1011263"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2020R1C1C1011263"],"award-info":[{"award-number":["NRF-2020R1C1C1011263"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and\u00a0Objectives: This study aimed to identify the analgesic properties of immature Rubus occidentalis extract (iROE) using a postoperative-pain rat model. We also aimed to compare the analgesic effects of iROE to those of mature R. occidentalis extract (mROE) and examine the proinflammatory cytokine response and associated underlying mechanisms. Materials and Methods: In adult male Sprague Dawley rats, acute postoperative pain was induced through plantar hind-paw incisions. After the plantar incisions were made, the rats were intraperitoneally administered with normal saline or various doses of iROE and mROE to investigate and compare the analgesic effects of iROE and mROE. The mechanisms underlying iROE-induced analgesia were investigated via post-incisional administration of yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine, followed by iROE. Mechanical withdrawal threshold (MWT) evaluations with von Frey filaments were carried out at different time points. Serum levels of tumor necrosis factor \u03b1, interleukin (IL)\u20131\u03b2, and IL-6 were measured to assess inflammatory responses. Multivariate analysis of variance (MANOVA) and linear mixed-effects model (LMEM) analysis were used to analyze the analgesic effect data. Results: The MWTs demonstrated significant increases in iROE in a dose-dependent manner up to 2 h after the plantar incisions were made. An LMEM analysis demonstrated that iROE yielded a significantly greater analgesic effect than mROE, but there was no significant difference between the two according to MANOVA. Dexmedetomidine enhanced the MWT-confirmed iROE response, while yohimbine and naloxone diminished it. Administration of iROE significantly attenuated the post-incisional increases in serum IL-1\u03b2 and IL-6 levels. Conclusions: The iROE demonstrated analgesic and anti-inflammatory effects in a rat model of incisional pain, which were more pronounced than those associated with mROE. The analgesic activity of iROE may be associated with \u03b12-adrenergic and opioid receptors.<\/jats:p>","DOI":"10.3390\/medicina59020264","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T04:58:25Z","timestamp":1675054705000},"page":"264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Immature Rubus occidentalis on Postoperative Pain in a Rat Model"],"prefix":"10.3390","volume":"59","author":[{"given":"Geun Joo","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, Seoul 06911, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2844-5880","authenticated-orcid":false,"given":"Hyun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, Seoul 06911, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oh Haeng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, Seoul 06911, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Wung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Gochang Berry & Bio Food Research Institute, Gochang 56417, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1002\/bjs.11477","article-title":"Acute postoperative pain management","volume":"107","author":"Small","year":"2020","journal-title":"Br. J. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1185\/03007995.2013.860019","article-title":"Incidence, patient satisfaction, and perceptions of post-surgical pain: Results from a US national survey","volume":"30","author":"Gan","year":"2014","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.2147\/JPR.S144066","article-title":"Poorly controlled postoperative pain: Prevalence, consequences, and prevention","volume":"10","author":"Gan","year":"2017","journal-title":"J. Pain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1097\/ALN.0000000000002238","article-title":"Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations","volume":"129","author":"Capdevila","year":"2018","journal-title":"Anesthesiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0952-8180(01)00320-8","article-title":"Multimodal analgesia for postoperative pain control","volume":"13","author":"Jin","year":"2001","journal-title":"J. Clin. Anesth."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1080\/01635581.2016.1115095","article-title":"Rubus occidentalis: The black raspberry\u2014Its potential in the prevention of cancer","volume":"68","author":"Kula","year":"2016","journal-title":"Nutr. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.scienta.2008.05.005","article-title":"Phytochemical accumulation and antioxidant capacity at four maturity stages of cranberry fruit","volume":"117","author":"Kaya","year":"2008","journal-title":"Sci. Hortic."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Samaniego, I., Brito, B., Viera, W., Cabrera, A., Llerena, W., Kannangara, T., Vilcacundo, R., Ang\u00f3s, I., and Carrillo, W. (2020). Influence of the Maturity Stage on the Phytochemical Composition and the Antioxidant Activity of Four Andean Blackberry Cultivars (Rubus glaucus Benth) from Ecuador. Plants, 9.","DOI":"10.3390\/plants9081027"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jss.2016.08.005","article-title":"Rubus occidentalis analgesic effect in a rat model of incisional pain","volume":"206","author":"Choi","year":"2016","journal-title":"J. Surg. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0304-3959(95)01441-1","article-title":"Characterization of a rat model of incisional pain","volume":"64","author":"Brennan","year":"1996","journal-title":"Pain"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kilkenny, C., Browne, W.J., Cuthill, I.C., Emerson, M., and Altman, D.G. (2010). Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000412"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/jpbs.JPBS_175_19","article-title":"Preparation of Medicinal Plants: Basic Extraction and Fractionation Procedures for Experimental Purposes","volume":"12","author":"Abubakar","year":"2020","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1213\/01.ane.0b013e31816ba437","article-title":"Sex, gender, and pain: An overview of a complex field","volume":"107","author":"Hurley","year":"2008","journal-title":"Anesth. Analg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"242","DOI":"10.30802\/AALAS-JAALAS-19-000084","article-title":"Review of Rodent Euthanasia Methods","volume":"59","author":"Shomer","year":"2020","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.lfs.2004.08.008","article-title":"Antinociceptive and gastroprotective effects of inhaled and orally administered Lavandula hybrida Reverchon \u201cGrosso\u201d essential oil","volume":"76","author":"Barocelli","year":"2004","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120820","DOI":"10.1093\/ecam\/nep144","article-title":"Antinociceptive Activity of Trichilia catigua Hydroalcoholic Extract: New Evidence on Its Dopaminergic Effects","volume":"2011","author":"Viana","year":"2011","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/2191-2858-2-18","article-title":"Attenuation of visceral nociception by \u03b1-bisabolol in mice: Investigation of mechanisms","volume":"2","author":"Gde","year":"2012","journal-title":"Org. Med. Chem. Lett."},{"key":"ref_18","first-page":"1190","article-title":"Preclinical efficacy of Dexmedetomidine on spinal cord injury provoked oxidative renal damage","volume":"37","year":"2015","journal-title":"Ren. Fail."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4097\/kjae.2004.46.6.719","article-title":"The Effect of an Intraperitoneal Injection of Ketamine and Ketorolac on Mechanical Allodynia in Rats with Spinal Nerve Ligation","volume":"46","author":"Kim","year":"2004","journal-title":"Korean J. Anesthesiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/1097-4598(200101)24:1<37::AID-MUS4>3.0.CO;2-8","article-title":"Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia","volume":"24","author":"Sluka","year":"2001","journal-title":"Muscle Nerve"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Golovinskaia, O., and Wang, C.K. (2021). Review of Functional and Pharmacological Activities of Berries. Molecules, 26.","DOI":"10.3390\/molecules26133904"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ygyno.2011.07.023","article-title":"A black raspberry extract inhibits proliferation and regulates apoptosis in cervical cancer cells","volume":"123","author":"Zhang","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"345","DOI":"10.4097\/kja.d.18.00217","article-title":"Designing the ideal perioperative pain management plan starts with multimodal analgesia","volume":"71","author":"Schwenk","year":"2018","journal-title":"Korean J. Anesthesiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"196","DOI":"10.2174\/1574886311666160426130444","article-title":"Efficacy and Safety of Nonopioid Analgesics in Perioperative Pain Control","volume":"11","author":"Thomas","year":"2016","journal-title":"Curr. Drug Saf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e013337","DOI":"10.1136\/bmjopen-2016-013337","article-title":"Dietary phytochemical intake from foods and health outcomes: A systematic review protocol and preliminary scoping","volume":"7","author":"Probst","year":"2017","journal-title":"BMJ Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1021\/jf1023388","article-title":"Effect of black raspberry (Rubus occidentalis L.) extract variation conditioned by cultivar, production site, and fruit maturity stage on colon cancer cell proliferation","volume":"59","author":"Johnson","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Choi, G.J., Kang, H., Lee, O.H., Ahn, E.J., White, F.A., Cho, Y.J., Baek, C.W., Jung, Y.H., and Kwon, J.W. (2022). Effectiveness of maturity of Rubus occidentalis on hyperalgesia induced by acidic saline injection in rats. BMC Complement. Med. Ther., 22.","DOI":"10.1186\/s12906-021-03491-z"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8021","DOI":"10.1021\/jf048619y","article-title":"Influence of cultivar, maturity, and sampling on blackberry (Rubus L. Hybrids) anthocyanins, polyphenolics, and antioxidant properties","volume":"52","author":"Siriwoharn","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s12298-018-0550-3","article-title":"Impact of maturity on phenolic composition and antioxidant activity of medicinally important leaves of Ficus carica L.","volume":"24","author":"Nadeem","year":"2018","journal-title":"Physiol. Mol. Biol. Plants"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S1054","DOI":"10.1080\/15538362.2020.1774476","article-title":"Role of maturity stages on phenolic compounds and organic acids contents in red currant fruits","volume":"20","author":"Berk","year":"2020","journal-title":"Int. J. Fruit Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4103\/0250-474X.106062","article-title":"Immature Rubus coreanus Shows a Free Radical-Scavenging Effect and Inhibits Cholesterol Synthesis and Secretion in Liver Cells","volume":"74","author":"Bhandary","year":"2012","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.fas.2018.05.001","article-title":"Role of anti-oxidant (vitamin-C) in post-operative pain relief in foot and ankle trauma surgery: A prospective randomized trial","volume":"25","author":"Jain","year":"2019","journal-title":"Foot Ankle Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9147279","DOI":"10.1155\/2016\/9147279","article-title":"Effect of Intravenous High Dose Vitamin C on Postoperative Pain and Morphine Use after Laparoscopic Colectomy: A Randomized Controlled Trial","volume":"2016","author":"Jeon","year":"2016","journal-title":"Pain Res. Manag."},{"key":"ref_34","first-page":"135","article-title":"Antioxidant therapy: A new pharmacological approach in shock, inflammation, and ischemia\/reperfusion injury","volume":"53","author":"Cuzzocrea","year":"2001","journal-title":"Pharmacol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Seo, K.H., Lee, J.Y., Park, J.Y., Jang, G.Y., Kim, H.D., Lee, Y.S., and Kim, D.H. (2019). Differences in anti-inflammatory effect of immature and mature of Rubus coreanus fruits on LPS-induced RAW 264.7 macrophages via NF-\u03baB signal pathways. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2496-6"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e588","DOI":"10.1097\/PR9.0000000000000588","article-title":"Postoperative pain-from mechanisms to treatment","volume":"2","author":"Segelcke","year":"2017","journal-title":"Pain Rep."},{"key":"ref_37","first-page":"Cd013263","article-title":"Single-dose intravenous ketorolac for acute postoperative pain in adults","volume":"5","author":"McNicol","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_38","first-page":"12","article-title":"Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies?","volume":"37","author":"Archie","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"c332","DOI":"10.1136\/bmj.c332","article-title":"CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials","volume":"340","author":"Schulz","year":"2010","journal-title":"BMJ"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/2\/264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:41Z","timestamp":1760120381000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/2\/264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,30]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["medicina59020264"],"URL":"https:\/\/doi.org\/10.3390\/medicina59020264","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2023,1,30]]}}}