{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T11:42:00Z","timestamp":1772365320835,"version":"3.50.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012921","name":"Royal College of Surgeons in Ireland","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012921","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Colorectal Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Haemorrhoids are one of the most frequently encountered benign anorectal conditions that negatively impact patients\u2019 quality of life. Excisional haemorrhoidectomy (closed or open) is a surgical procedure reserved for the treatment of third- and fourth-degree haemorrhoids, with considerable post-procedure pain reported. The aim of this study was to clarify the association between post operative metronidazole use (both oral and topical) and post-haemorrhoidectomy pain scores through systematic review and meta-analysis of randomised controlled trials (RCTs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Prospective registration was performed on PROSPERO (CRD42024580928). A systematic review was performed for RCTs reporting post-haemorrhoidectomy pain scores between patients who received metronidazole and patients who received placebo. Meta-analysis was performed using RevMan version 5.4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventeen RCTs including 1297 participants were eligible for inclusion. Metronidazole administration was associated with significantly lower post-operative visual analogue scores (VAS) on day 1 (\u22121.18,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.00001), day 2 (\u22121.15,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), day 3 (\u22120.86,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.00001), and day 7 post-operatively with a mean pain score difference of \u22121.72 (95% CI \u22122.27 to \u22121.18) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.00001). A significant difference in pain scores was seen on day 3 favouring topical metronidazole in comparison to the oral route (1.38, 95% CI [0.44, 2.32],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This review synthesises the best available evidence to support the use of metronidazole to reduce pain after excisional haemorrhoidectomy. While both oral and topical forms appear to be beneficial, topical administration appears to have a more effective analgesic effect from post-operative day 3.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00384-025-05066-7","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T13:14:58Z","timestamp":1769433298000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metronidazole is an effective method of analgesia following haemorrhoidectomy: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"41","author":[{"given":"Aaron","family":"O\u2019Mahony","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Cullinane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin M.","family":"MacCurtain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Peirce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eoghan","family":"Condon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Calvin","family":"Coffey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina A.","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"issue":"1","key":"5066_CR1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/s41598-021-03838-z","volume":"12","author":"YS Hong","year":"2022","unstructured":"Hong YS, Jung KU, Rampal S, Zhao D, Guallar E, Ryu S et al (2022) Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults. Sci Rep 12(1):129","journal-title":"Sci Rep"},{"issue":"17","key":"5066_CR2","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.3748\/wjg.v18.i17.2009","volume":"18","author":"V Lohsiriwat","year":"2012","unstructured":"Lohsiriwat V (2012) Hemorrhoids: from basic pathophysiology to clinical management. World J Gastroenterol 18(17):2009\u20132017","journal-title":"World J Gastroenterol"},{"key":"5066_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2021.729166","volume":"8","author":"S De Marco","year":"2021","unstructured":"De Marco S, Tiso D (2021) Lifestyle and risk factors in hemorrhoidal disease. Front Surg 8:729166","journal-title":"Front Surg"},{"key":"5066_CR4","doi-asserted-by":"crossref","unstructured":"Heah S-M (2004) Acute management of haemorrhoids. Acute Surgical Management:461","DOI":"10.1142\/9789812563033_0028"},{"key":"5066_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58030418","author":"V Lohsiriwat","year":"2022","unstructured":"Lohsiriwat V, Jitmungngan R (2022) Strategies to reduce post-hemorrhoidectomy pain: a systematic review. Medicina (Kaunas). https:\/\/doi.org\/10.3390\/medicina58030418","journal-title":"Medicina (Kaunas)"},{"issue":"9","key":"5066_CR6","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1111\/codi.13755","volume":"19","author":"NJR Lyons","year":"2017","unstructured":"Lyons NJR, Cornille JB, Pathak S, Charters P, Daniels IR, Smart NJ (2017) Systematic review and meta-analysis of the role of metronidazole in post-haemorrhoidectomy pain relief. Colorectal Dis 19(9):803\u2013811","journal-title":"Colorectal Dis"},{"issue":"9097","key":"5066_CR7","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S0140-6736(97)09003-X","volume":"351","author":"EA Carapeti","year":"1998","unstructured":"Carapeti EA, Kamm MA, McDonald PJ, Phillips RK (1998) Double-blind randomised controlled trial of effect of metronidazole on pain after day-case haemorrhoidectomy. Lancet 351(9097):169\u2013172","journal-title":"Lancet"},{"issue":"11","key":"5066_CR8","doi-asserted-by":"publisher","first-page":"3077","DOI":"10.1021\/acschembio.2c00462","volume":"17","author":"T Reinhardt","year":"2022","unstructured":"Reinhardt T, Lee KM, Niederegger L, Hess CR, Sieber SA (2022) Indolin-2-one nitroimidazole antibiotics exhibit an unexpected dual mode of action. ACS Chem Biol 17(11):3077\u20133085","journal-title":"ACS Chem Biol"},{"key":"5066_CR9","doi-asserted-by":"crossref","unstructured":"Solorio-L\u00f3pez S, Palomares-Chac\u00f3n UR, Guerrero-Tar\u00edn JE, Gonz\u00e1lez-Ojeda A, Cort\u00e9s-Lares JA, Rend\u00f3n-F\u00e9lix J, et al. (2015) Efficacy of metronidazole versus placebo in pain control after hemorrhoidectomy. Results of a controlled clinical trial. Rev Esp Enferm Dig. 107(11):681\u20135.","DOI":"10.17235\/reed.2015.3926\/2015"},{"issue":"1","key":"5066_CR10","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13643-021-01626-4","volume":"10","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev 10(1):89","journal-title":"Syst Rev"},{"key":"5066_CR11","unstructured":"A E, Z F, H H, I I, M K, M O. Rayyan: a systematic reviews web app for exploring and filtering searches for eligible studies for Cochrane Reviews, p 9"},{"issue":"2","key":"5066_CR12","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/S0039-6109(05)70381-9","volume":"79","author":"J Katz","year":"1999","unstructured":"Katz J, Melzack R (1999) Measurement of pain. Surg Clin North Am 79(2):231\u2013252","journal-title":"Surg Clin North Am"},{"key":"5066_CR13","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928","volume":"343","author":"JPT Higgins","year":"2011","unstructured":"Higgins JPT, Altman DG, G\u00f8tzsche PC, J\u00fcni P, Moher D, Oxman AD et al (2011) The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials. BMJ 343:d5928","journal-title":"BMJ"},{"key":"5066_CR14","unstructured":"Higgins JPT TJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane handbook for systematic reviews of interventions: Cochrane; 2023 [updated Aug 2023. version 6.4:[Available from: www.training.cochrane.org\/handbook."},{"issue":"6","key":"5066_CR15","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1177\/0962280216669183","volume":"27","author":"D Luo","year":"2018","unstructured":"Luo D, Wan X, Liu J, Tong T (2018) Optimally estimating the sample mean from the sample size, median, mid-range, and\/or mid-quartile range. Stat Methods Med Res 27(6):1785\u20131805","journal-title":"Stat Methods Med Res"},{"key":"5066_CR16","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/1471-2288-14-135","volume":"14","author":"X Wan","year":"2014","unstructured":"Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range. BMC Med Res Methodol 14:135","journal-title":"BMC Med Res Methodol"},{"issue":"1","key":"5066_CR17","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1111\/codi.15291","volume":"23","author":"BD Wilkie","year":"2021","unstructured":"Wilkie BD, Chandra R, Chua J, Lam DCS, Paratz ED, An V et al (2021) Efficacy of postoperative oral metronidazole for haemorrhoidectomy pain: a randomized double-blind, placebo-controlled trial. Colorectal Dis 23(1):274\u2013282","journal-title":"Colorectal Dis"},{"key":"5066_CR18","doi-asserted-by":"crossref","unstructured":"Balfour L, Stojkovic SG, Botterill ID, Burke DA, Finan PJ, Sagar PM. (2002) A randomized, double-blind trial of the effect of metronidazole on pain after closed hemorrhoidectomy. Dis Colon Rectum. 45(9):1186\u201390; discussion 90\u20131.","DOI":"10.1007\/s10350-004-6390-y"},{"issue":"5","key":"5066_CR19","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s10350-003-0129-z","volume":"47","author":"TJ Nicholson","year":"2004","unstructured":"Nicholson TJ, Armstrong D (2004) Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing. Dis Colon Rectum 47(5):711\u2013716","journal-title":"Dis Colon Rectum"},{"issue":"2","key":"5066_CR20","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s10350-007-9174-3","volume":"51","author":"S Ala","year":"2008","unstructured":"Ala S, Saeedi M, Eshghi F, Mirzabeygi P (2008) Topical metronidazole can reduce pain after surgery and pain on defecation in postoperative hemorrhoidectomy. Dis Colon Rectum 51(2):235\u2013238","journal-title":"Dis Colon Rectum"},{"issue":"3","key":"5066_CR21","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/j.1744-1633.2006.00308.x","volume":"10","author":"SS-M Ng","year":"2006","unstructured":"Ng SS-M, Lee JF-Y, Cheung K-Y, Leung K-L, Yiu RY-C, Lau W-Y (2006) Pre-emptive analgesia and metronidazole on post-haemorrhoidectomy pain control. Surg Pract 10(3):102\u2013105","journal-title":"Surg Pract"},{"issue":"8","key":"5066_CR22","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s10151-021-02465-0","volume":"25","author":"FEF Rabelo","year":"2021","unstructured":"Rabelo FEF, Lacerda-Filho A, Mansur ES, de Oliveira FH, de Queiroz FL, Fran\u00e7a-Neto PR et al (2021) Benefits of flavonoid and metronidazole use after excisional hemorrhoidectomy: a randomized double-blind clinical trial. Tech Coloproctol 25(8):949\u2013955","journal-title":"Tech Coloproctol"},{"issue":"11","key":"5066_CR23","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1097\/DCR.0000000000002163","volume":"65","author":"W Xia","year":"2022","unstructured":"Xia W, Barazanchi AWH, MacFater WS, MacCormick AD, Svirskis D, Sammour T et al (2022) Topical versus oral metronidazole after excisional hemorrhoidectomy: a double-blind randomized controlled trial. Dis Colon Rectum 65(11):1362\u20131372","journal-title":"Dis Colon Rectum"},{"key":"5066_CR24","doi-asserted-by":"publisher","first-page":"3598","DOI":"10.18203\/2349-2902.isj20184629","volume":"5","author":"P Neogi","year":"2018","unstructured":"Neogi P, Sinha A, Singh M (2018) Is metronidazole a panacea for post-hemorrhoidectomy pain? Int Surg J 5:3598","journal-title":"Int Surg J"},{"issue":"5","key":"5066_CR25","doi-asserted-by":"publisher","first-page":"867","DOI":"10.12669\/pjms.36.5.1796","volume":"36","author":"ST Abbas","year":"2020","unstructured":"Abbas ST, Raza A, Muhammad Ch I, Hameed T, Hasham N, Arshad N (2020) Comparison of mean pain score using topical and oral metronidazole in post milligan morgan hemorrhoidectomy patient; a randomized controlled trial. Pak J Med Sci 36(5):867\u2013871","journal-title":"Pak J Med Sci"},{"key":"5066_CR26","unstructured":"Munawar Islam S, Zafar M, Azhar M, Ali M, Ali H (2023) The efficacy of oral metronidazole in reducing pain post- hemorrhoidectomy: a randomized controlled trial. Medical Forum Monthly"},{"key":"5066_CR27","unstructured":"Razzaq S, Khan Z, Mahmood MA, Khan MN, Iqbal W, Zareen N (eds) (2020) Comparison of effectiveness of topical and oral metronidazole for reducing postoperative pain after hemorrhoidectomy. Medical Forum Monthly"},{"issue":"2","key":"5066_CR28","doi-asserted-by":"publisher","first-page":"90","DOI":"10.48036\/apims.v19i2.782","volume":"19","author":"G Rooh Ali","year":"2023","unstructured":"Rooh Ali G, Sughra P, Dileep K, Kanwal H, Abdul W, Jahangir Ali S (2023) Comparative study of placebo versus metronidazole as a role of pain relief post hemorrhoidectomy. Annals of PIMS-Shaheed Zulfiqar Ali Bhutto Medical University 19(2):90\u201393","journal-title":"Annals of PIMS-Shaheed Zulfiqar Ali Bhutto Medical University"},{"issue":"10","key":"5066_CR29","first-page":"1538","volume":"27","author":"AS Al-Mulhim","year":"2006","unstructured":"Al-Mulhim AS, Ali AM, Al-Masuod N, Alwahidi A (2006) Post hemorrhoidectomy pain. A randomized controlled trial. Saudi Med J 27(10):1538\u20131541","journal-title":"Saudi Med J"},{"key":"5066_CR30","unstructured":"Abdullah AAK, Panthi R, Devangan M. (2024) Comparative study between oral and topical metronidazole in early recovery from pain after open haemorrhoidectomy. International Journal of Science and Research.\u00a0"},{"issue":"3","key":"5066_CR31","first-page":"640","volume":"50","author":"F Firdous","year":"2025","unstructured":"Firdous F, Arsalan S, Siddique S, Shahzad R, Rasheed G, Khan JS (2025) Comparison of 10% topical metronidazole versus oral metronidazole in hemorrhoidectomy in terms of post-operative pain. Rawal Med J 50(3):640","journal-title":"Rawal Med J"},{"issue":"8","key":"5066_CR32","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1007\/BF02050347","volume":"34","author":"PR de Paula","year":"1991","unstructured":"de Paula PR, Speranzini MB, Hamzagic HC, Bassi DG, Chacon-Silva MA, Novo NF et al (1991) Bacteriology of the anal wound after open hemorrhoidectomy. Qualitative and quantitative analysis. Dis Colon Rectum 34(8):664\u2013669","journal-title":"Dis Colon Rectum"},{"issue":"7","key":"5066_CR33","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.intimp.2010.04.004","volume":"10","author":"A Rizzo","year":"2010","unstructured":"Rizzo A, Paolillo R, Guida L, Annunziata M, Bevilacqua N, Tufano MA (2010) Effect of metronidazole and modulation of cytokine production on human periodontal ligament cells. Int Immunopharmacol 10(7):744\u2013750","journal-title":"Int Immunopharmacol"},{"issue":"4","key":"5066_CR34","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1111\/omi.12459","volume":"39","author":"LJ Su\u00e1rez","year":"2024","unstructured":"Su\u00e1rez LJ, Arce RM, Gon\u00e7alves C, Furquim CP, Santos NCD, Retamal-Valdes B et al (2024) Metronidazole may display anti-inflammatory features in periodontitis treatment: a scoping review. Mol Oral Microbiol 39(4):240\u2013259","journal-title":"Mol Oral Microbiol"},{"issue":"1","key":"5066_CR35","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41380-020-0661-4","volume":"26","author":"ND Volkow","year":"2021","unstructured":"Volkow ND, Blanco C (2021) The changing opioid crisis: development, challenges and opportunities. Mol Psychiatry 26(1):218\u2013233","journal-title":"Mol Psychiatry"},{"key":"5066_CR36","doi-asserted-by":"publisher","DOI":"10.1097\/DCR.0000000000000792","author":"KN Wanis","year":"2017","unstructured":"Wanis KN, Emmerton-Coughlin HM, Coughlin S, Foley N, Vinden C (2017) Systemic metronidazole may not reduce posthemorrhoidectomy pain: a meta-analysis of randomized controlled trials. Dis Colon Rectum. https:\/\/doi.org\/10.1097\/DCR.0000000000000792","journal-title":"Dis Colon Rectum"},{"key":"5066_CR37","doi-asserted-by":"crossref","unstructured":"Bikfalvi A, Faes C, Freys SM, Joshi GP, Van de Velde M, Albrecht E.(2023) PROSPECT guideline for haemorrhoid surgery: a systematic review and procedure-specific postoperative pain management recommendations. European Journal of Anaesthesiology and Intensive Care. 2(3):e0023","DOI":"10.1097\/EA9.0000000000000023"},{"issue":"2","key":"5066_CR38","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s00268-016-3737-1","volume":"41","author":"T Sammour","year":"2017","unstructured":"Sammour T, Barazanchi AW, Hill AG (2017) Evidence-based management of pain after excisional haemorrhoidectomy surgery: a PROSPECT review update. World J Surg 41(2):603\u2013614","journal-title":"World J Surg"},{"issue":"9","key":"5066_CR39","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1097\/DCR.0000000000003419","volume":"67","author":"JZ Jin","year":"2024","unstructured":"Jin JZ, Xia W, Gao R, Vandal AC, Weston M, Israel L et al (2024) A randomized controlled trial of topical analgesia posthemorrhoidectomy (TAPH trial). Dis Colon Rectum 67(9):1158\u20131168","journal-title":"Dis Colon Rectum"}],"container-title":["International Journal of Colorectal Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00384-025-05066-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00384-025-05066-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00384-025-05066-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:34:55Z","timestamp":1769474095000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00384-025-05066-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5066"],"URL":"https:\/\/doi.org\/10.1007\/s00384-025-05066-7","relation":{},"ISSN":["1432-1262"],"issn-type":[{"value":"1432-1262","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]},"assertion":[{"value":"6 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2026","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"}}],"article-number":"42"}}