The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation

Abstract

Background: Surgical procedures cause perioperative immunosuppression and neuroendocrine stress, exerted by activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. 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 versus a combination of the non-selective Cox inhibitor; diclofenac, with neostigmine; in different experimental models of analgesia and inflammation in rats.Methods: 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 β-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.Results: 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 β-endorphin, TNF-α, NF-кB 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. Conclusion: 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.

Efficacy and safety of preoperative versus postoperative NSAIDs on pain relief in patients undergoing hip arthroscopy surgery: A multicentre, randomized, controlled trial

“…The present study disclosed that preoperative administration of NSAIDs reduced FAI patients' pain at rest (at D1 and D2) and pain at movement (at D1, D2, and D3) compared to postoperative administration. The possible argument would be that: the utilization of NSAIDs before HAS allowed the earlier achievement of steady‐state concentration of NSAIDs compared with the postoperative administration, thus, preoperative use of NSAIDs had a better short‐term analgesic effect compared to its postoperative utilization in FAI patients 21–23 . However, the steady‐state concentrations of NSAIDs were reached over time with either its preoperative or postoperative use, so the analgesic effects were similar at D7 among these two groups.…”