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The acetylcholinesterase inhibitor (ACHEI); neostigmine, is known clinically for its analgesic effect in the perioperative phases proving high efficacy; besides possessing anti-inflammatory properties controlling immune cells and cytokine level. Hence, this study evaluated and compared the analgesic and anti-inflammatory activities of the combination of selective Cox-2 inhibitor; celecoxib, with neostigmine\n                      <jats:italic>versus<\/jats:italic>\n                      a combination of the non-selective Cox inhibitor; diclofenac, with neostigmine; in different experimental models of analgesia and inflammation in rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Analgesic activity of neostigmine with\/without diclofenac or celecoxib was assessed in female Sprague-Dawely rats using the tail clip model and acetic acid induced writhing. Serum level of \u03b2-endorphin was assessed after the tail clip test. The anti-inflammatory activity was evaluated using acute and sub-chronic formalin induced paw edema. At the end of the sub-chronic formalin test, blood samples were collected for analysis of anti-inflammatory, liver and kidney function markers. Livers, kidneys and hind paws were also examined histopathologically.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Addition of neostigmine to selective or non-selective NSAIDs (celecoxib or diclofenac) causes an increased level of analgesia of NSAIDs with rapid onset of action and short duration, while causing potentiation of the anti-inflammatory effect of neostigmine as seen in the tail clip, writhing, formalin test, Cox-1 and Cox-2 activities, serum \u03b2-endorphin, TNF-\u03b1, NF-\u043aB and HS-CRP. All combinations of this study disturb some kidney and liver functions, however with normal histopathological appearances, while hind paws reveal improved inflammatory infiltration in all treated groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Selective and non-selective NSAIDs examined in this study could be good adjunct options to general anesthetic agents and neostigmine in perioperative stages, an outcome that needs further clinical investigations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-021-00488-9","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T07:43:03Z","timestamp":1620027783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The effective interplay of (non-) selective NSAIDs with neostigmine in animal models of analgesia and inflammation"],"prefix":"10.1186","volume":"22","author":[{"given":"Mennatallah A","family":"Gowayed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amany","family":"Abdel-Bary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasha A","family":"El-Tahan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"488_CR1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0090-6980(02)00027-8","volume":"68","author":"LJ Marnett","year":"2002","unstructured":"Marnett LJ. 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