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This study investigated the roles of bromelain against pro-inflammatory mediators as a mechanism that underpins its antinociceptive and anti-anxiety effects in the peripheral model of NP. Sixty-four male <jats:italic>Wistar<\/jats:italic> rats randomly divided into eight groups, were used for the study. A chronic constriction injury model of peripheral neuropathy was used to induce NP. Tail-immersion and von Frey filaments tests were used to assess hyperalgesia while open field and elevated plus mazes were used to assess anxiety-like behaviour. NF-\u043aB, iNOS, nitrate, and pro-inflammatory cytokines were investigated in the plasma, sciatic nerve, and brain tissues using ELISA, spectrophotometer, and immunohistochemistry techniques after twenty-one days of treatment. Bromelain significantly (p\u2009&lt;\u20090.05) improved the cardinal signs of NP and inhibited anxiety-like behaviours in ligated Wistar rats. It mitigated the increases in cerebral cortex interleukin (IL) -1\u03b2, IL-6, and PGE<jats:sub>2<\/jats:sub> levels. Bromelain reduced NF-\u043aB, IL-1\u03b2, IL-6, TNF-\u03b1, PGE<jats:sub>2,<\/jats:sub> and nitrate concentrations as well as the expression of iNOS in the sciatic nerve. Hence, the antinociceptive and anxiolytic effects of bromelain in the sciatic nerve ligation model of NP is in part due to its ability to reduce nitrosative and inflammatory activities.<\/jats:p>","DOI":"10.1038\/s41598-020-79421-9","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T11:25:44Z","timestamp":1610364344000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Bromelain reduced pro-inflammatory mediators as a common pathway that mediate antinociceptive and anti-anxiety effects in sciatic nerve ligated Wistar rats"],"prefix":"10.1038","volume":"11","author":[{"given":"Ahmed O.","family":"Bakare","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bamidele V.","family":"Owoyele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"79421_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.cyto.2012.03.027","volume":"59","author":"XM Wang","year":"2012","unstructured":"Wang, X. 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