{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T18:07:31Z","timestamp":1784830051655,"version":"3.55.0"},"reference-count":71,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Secretary of Science, Humanities, Technology and Innovation","award":["1143882"],"award-info":[{"award-number":["1143882"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Neuropathic pain (NP) after traumatic spinal cord injury (SCI) is highly prevalent, markedly impairs quality of life, and remains difficult to treat because available therapies show limited efficacy and may cause relevant adverse effects. Because oxidative stress and glutamate-mediated excitotoxicity contribute to central sensitization after SCI, this study evaluated the antinociceptive and antioxidant effects of dapsone (DDS), N-acetylcysteine (NAC), and their combination in rats with SCI. An isobolographic analysis was also performed to determine the pharmacodynamic interaction between the two drugs. Methods: Female Wistar rats with SCI that developed stimulus-dependent hypersensitivity from day 15 after injury were treated once daily for 7 days with DDS (1.5\u201312.5 mg\/kg, i.p.), NAC (9.3\u201375 mg\/kg, i.p.), or 1:1 fixed-ratio combinations. Mechanical allodynia and hyperalgesia were assessed with Von Frey filaments, whereas lipid peroxidation (LP) and reduced glutathione (GSH) were quantified in injured spinal cord tissue. Results: DDS and NAC produced dose-dependent antinociceptive effects, with DDS being more potent than NAC in both endpoints. The individual ED50 values were 4.92 and 33.47 mg\/kg for allodynia, and 4.06 and 27.74 mg\/kg for hyperalgesia, for DDS and NAC, respectively. The DDS\/NAC combination showed synergistic interactions in allodynia (ED50 = 7.45 mg\/kg vs. Zadd = 19.19 mg\/kg; \u03b3 = 0.388) and hyperalgesia (ED50 = 4.21 mg\/kg vs. Zadd = 15.90 mg\/kg; \u03b3 = 0.265), with stronger synergism in hyperalgesia. Combined treatment also improved LP and GSH levels. Conclusions: These findings indicate that DDS and NAC exert complementary actions and that their combination produces a synergistic antinociceptive effect associated with diminished oxidative stress after SCI.<\/jats:p>","DOI":"10.3390\/brainsci16080777","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dapsone and N-Acetylcysteine Exert a Synergistic Antinociceptive Effect Associated with Oxidative Stress After Traumatic Spinal Cord Injury: An Isobolographic Study"],"prefix":"10.3390","volume":"16","author":[{"given":"H\u00e9ctor Alonso","family":"Romero-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Maestr\u00eda y Doctorado en Ciencias Farmac\u00e9uticas, Universidad Aut\u00f3noma Metropolitana Unidad Xochimilco, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3216-0119","authenticated-orcid":false,"given":"Camilo","family":"R\u00edos","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Neurociencias, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"},{"name":"Laboratorio de Neurofarmacolog\u00eda Molecular, Departamento de Sistemas Biol\u00f3gicos, Universidad Aut\u00f3noma Metropolitana, Unidad Xochimilco, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda de los \u00c1ngeles","family":"Mart\u00ednez-C\u00e1rdenas","sequence":"additional","affiliation":[{"name":"Departamento de Atenci\u00f3n a la Salud, \u00c1rea de investigaci\u00f3n: Estados y Servicios de Salud, Universidad Aut\u00f3noma Metropolitana Unidad Xochimilco, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-0871","authenticated-orcid":false,"given":"Luz","family":"Navarro","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1021-4884","authenticated-orcid":false,"given":"Luis Alfonso","family":"Moreno-Rocha","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Traslacional, Departamento de Sistemas Biol\u00f3gicos, Universidad Aut\u00f3noma Metropolitana, Unidad Xochimilco, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Mata-Bermudez","sequence":"additional","affiliation":[{"name":"Departamento de Atenci\u00f3n a la Salud, \u00c1rea de investigaci\u00f3n: Estados y Servicios de Salud, Universidad Aut\u00f3noma Metropolitana Unidad Xochimilco, Mexico City 04960, Mexico"},{"name":"Centro de Investigaci\u00f3n en Ciencias de la Salud (CICSA), FCS (Facultad de Ciencias de la Salud), Universidad An\u00e1huac M\u00e9xico Campus Norte, Huixquilucan 52786, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1481-0966","authenticated-orcid":false,"given":"Araceli","family":"D\u00edaz-Ruiz","sequence":"additional","affiliation":[{"name":"Departamento de Neuroqu\u00edmica, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda Manuel Velasco Suarez, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41393-021-00744-z","article-title":"The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update","volume":"60","author":"Loh","year":"2022","journal-title":"Spinal Cord"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s13311-018-0633-4","article-title":"Neuropathic Pain After Spinal Cord Injury: Challenges and Research Perspectives","volume":"15","author":"Shiao","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.cnc.2017.08.002","article-title":"The Role of Pain Classification Systems in Pain Management","volume":"29","author":"Orr","year":"2017","journal-title":"Crit. 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