{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:28:55Z","timestamp":1773264535216,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007104","name":"Trakya University","doi-asserted-by":"publisher","award":["2023.12.02"],"award-info":[{"award-number":["2023.12.02"]}],"id":[{"id":"10.13039\/501100007104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Duloxetine, a serotonin\u2013norepinephrine reuptake inhibitor, is widely used both preoperatively and postoperatively in patients with neuropathic low back pain. This study aimed to determine the impact of duloxetine administration on posterolateral spinal fusion in rats and to evaluate the dose-dependent relationship of this effect. Methods: A pre-established rat model for posterolateral spinal fusion was employed, and four equal groups were formed, each undergoing posterolateral spinal fusion surgery. Except for the control group, the other groups received duloxetine postoperatively starting on day 1 at doses of 30 mg\/kg\/day, 60 mg\/kg\/day, and 120 mg\/kg\/day for six weeks. All rats were sacrificed after six weeks. Fusion status was assessed using manual palpation, radiological examination with plain radiography, and histopathological evaluation.\u00a0Results: No significant differences were observed between groups in manual palpation scoring or radiological scoring. Histopathological evaluations of new bone formation also showed no significant differences between groups. The number of inflammatory cells was found to be higher in the control group compared to the low- and moderate-dose duloxetine groups (p = 0.012). Neovascularization scores were slightly higher in the control group compared to the duloxetine-treated groups (p = 0.048). Conclusions: In this experimental rat model of posterolateral spinal fusion, duloxetine administration was associated with reduced inflammatory cell infiltration and mildly decreased neovascularization on histopathological evaluation. However, these histological differences did not translate into measurable differences in fusion outcomes, as assessed by manual palpation, radiological scoring, or new bone formation. Overall, postoperative duloxetine treatment did not demonstrate a detrimental effect on spinal fusion success, suggesting that its use for neuropathic pain management may be biologically applicable with respect to fusion healing in this animal model.<\/jats:p>","DOI":"10.3390\/jcm15052087","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:49:42Z","timestamp":1773071382000},"page":"2087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Duloxetine on Fusion in Rats Undergoing Posterolateral Spinal Fusion"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0337-2913","authenticated-orcid":false,"given":"Ozan","family":"G\u00fcner","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Traumatology, Trakya University Faculty of Medicine, Balkan Campus, 22030 Edirne, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-5515","authenticated-orcid":false,"given":"Murat","family":"Erem","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Trakya University Faculty of Medicine, Balkan Campus, 22030 Edirne, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-2819","authenticated-orcid":false,"given":"Mert","family":"\u00c7iftdemir","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Trakya University Faculty of Medicine, Balkan Campus, 22030 Edirne, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ufuk","family":"Usta","sequence":"additional","affiliation":[{"name":"Department of Pathology, Trakya University Faculty of Medicine, Balkan Campus, 22030 Edirne, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nermin","family":"Tun\u00e7bilek","sequence":"additional","affiliation":[{"name":"Department of Radiology, Trakya University Faculty of Medicine, Balkan Campus, 22030 Edirne, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1097\/BLO.0b013e3180686b30","article-title":"An operation for progressive spinal deformities: A preliminary report of three cases from the service of the orthopaedic hospital","volume":"460","author":"Hibbs","year":"2007","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/BLO.0b013e3180686a0f","article-title":"Transplantation of a portion of the tibia into the spine for Pott\u2019s disease: A preliminary report","volume":"460","author":"Albee","year":"2007","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_3","unstructured":"National Institute for Health and Care Excellence (2020). Neuropathic Pain in Adults: Pharmacological Management in Non-Specialist Settings, National Institute for Health and Care Excellence (NICE)."},{"key":"ref_4","unstructured":"National Guideline Centre (UK) (2016). Low Back Pain and Sciatica in Over 16s: Assessment and Management, National Institute for Health and Care Excellence (NICE)."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/AAP.0b013e3181df2645","article-title":"Duloxetine: A review of its pharmacology and use in chronic pain management","volume":"35","author":"Bellingham","year":"2010","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1213\/ANE.0000000000002380","article-title":"Repeated Administration of Duloxetine Suppresses Neuropathic Pain by Accumulating Effects of Noradrenaline in the Spinal Cord","volume":"126","author":"Ito","year":"2018","journal-title":"Anesth. Analg."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yamashita, T., Yamamoto, S., Zhang, J., Kometani, M., Tomiyama, D., Kohno, K., Tozaki-Saitoh, H., Inoue, K., and Tsuda, M. (2016). Duloxetine Inhibits Microglial P2X4 Receptor Function and Alleviates Neuropathic Pain after Peripheral Nerve Injury. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165189"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1210\/jc.2010-0861","article-title":"Update in serotonin and bone","volume":"95","author":"Bliziotes","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/978-3-319-66653-2_3","article-title":"Regulation of bone metabolism by serotonin","volume":"Volume 1033","author":"Lavoie","year":"2017","journal-title":"Understanding the Gut-Bone Signaling Axis; Advances in Experimental Medicine and Biology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106481","DOI":"10.1016\/j.prostaglandins.2020.106481","article-title":"Duloxetine strengthens osteoblast activation by prostaglandin E1: Upregulation of p38 MAP kinase","volume":"151","author":"Tachi","year":"2020","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115810","DOI":"10.1016\/j.biopha.2023.115810","article-title":"Antidepressant duloxetine hydrochloride protects against ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation","volume":"168","author":"Zhou","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13461","DOI":"10.1038\/s41598-021-92821-9","article-title":"Use of serotonin reuptake inhibitors and risk of subsequent bone loss in a nationwide population-based cohort study","volume":"11","author":"Kang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/j.1468-1331.2009.02648.x","article-title":"A double-blind, randomized trial of duloxetine versus placebo in the management of chronic low back pain","volume":"16","author":"Skljarevski","year":"2009","journal-title":"Eur. J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1111\/papr.13253","article-title":"Postoperative acute pain management with duloxetine as compared to placebo: A systematic review with meta-analysis of randomized clinical trials","volume":"23","author":"Govil","year":"2023","journal-title":"Pain Pract."},{"key":"ref_15","first-page":"3","article-title":"Duloksetin farmakolojisi","volume":"12","year":"2009","journal-title":"Turk. J. Clin. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"151686","DOI":"10.1016\/j.soncn.2024.151686","article-title":"Prazosin as an Adjuvant to Increase Effectiveness of Duloxetine in a Rat Model of Oxaliplatin-Induced Peripheral Neuropathy","volume":"40","author":"Wagner","year":"2024","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2165\/11539240-000000000-00000","article-title":"Duloxetine: Clinical pharmacokinetics and drug interactions","volume":"50","author":"Knadler","year":"2011","journal-title":"Clin. Pharmacokinet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1007\/s00586-019-06226-4","article-title":"Effects of pregabalin on spinal fusion","volume":"29","year":"2020","journal-title":"Eur. Spine J."},{"key":"ref_19","first-page":"28","article-title":"Evaluation of postoperative analgesia in a rat model of incisional pain","volume":"42","author":"Stewart","year":"2003","journal-title":"Contemp. Top. Lab. Anim. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3340\/jkns.2009.46.1.45","article-title":"The effect of risedronate on posterior lateral spinal fusion in a rat model","volume":"46","author":"Gezici","year":"2009","journal-title":"J. Korean Neurosurg. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/00002517-199212000-00008","article-title":"Results of in situ fusion for isthmic spondylolisthesis","volume":"5","author":"Lenke","year":"1992","journal-title":"J. Spinal Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"540","DOI":"10.2106\/00004623-199404000-00008","article-title":"The biological and biomechanical effects of irradiation on anterior spinal bone grafts in a canine model","volume":"76","author":"Emery","year":"1994","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1097\/00007632-199512150-00004","article-title":"The use of an osteoinductive growth factor for lumbar spinal fusion. part II: Study of dose, carrier, and species","volume":"20","author":"Boden","year":"1995","journal-title":"Spine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.14245\/kjs.2017.14.2.35","article-title":"The therapeutic effects of combination therapy with curcumin and alendronate on spine fusion surgery in the ovariectomized rats","volume":"14","author":"Cho","year":"2017","journal-title":"Korean J. Spine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s00586-009-1263-7","article-title":"Nitric oxide modulates recombinant human bone morphogenetic protein-2-induced corticocancellous autograft incorporation: A study in rat intertransverse fusion","volume":"19","author":"Diwan","year":"2010","journal-title":"Eur. Spine J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/S0022-3565(24)37461-0","article-title":"Electrophysiological characterization of the effect of long-term duloxetine administration on the rat serotonergic and noradrenergic systems","volume":"285","author":"Rueter","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Agoston, D.V. (2017). How to Translate Time? The Temporal Aspect of Human and Rodent Biology. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00092"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.2174\/1381612053764805","article-title":"The dual transporter inhibitor duloxetine: A review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression","volume":"11","author":"Bymaster","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.neulet.2014.03.046","article-title":"The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration","volume":"568","author":"Sun","year":"2014","journal-title":"NeuroSci. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"F264","DOI":"10.1152\/ajprenal.90241.2008","article-title":"Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on sneeze-induced urethral continence reflex in rats","volume":"295","author":"Miyazato","year":"2008","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4142\/jvs.2014.15.2.289","article-title":"Comparable bone healing capacity of different bone graft matrices in a rabbit segmental defect model","volume":"15","author":"Kim","year":"2014","journal-title":"J. Vet. Sci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/5\/2087\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:27:33Z","timestamp":1773206853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/5\/2087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["jcm15052087"],"URL":"https:\/\/doi.org\/10.3390\/jcm15052087","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}