Abstract
BackgroundSurgical 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.MethodsAnalgesic 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.ResultsAddition 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.ConclusionsSelective 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.
Highlights
Surgical procedures cause perioperative immunosuppression and neuroendocrine stress, exerted by activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis
The known mechanism of Non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of the enzyme cyclooxygenase (Cox), which consists of two isoforms known as Cox-1 and Cox-2 [1], each has a different pattern of expression and function
It has been generally accepted that the inhibition of Cox mediates the anti-inflammatory, antipyretic and analgesic effects of NSAIDs [3], where analgesia has been associated with selective Cox-2 inhibition
Summary
Surgical procedures cause perioperative immunosuppression and neuroendocrine stress, exerted by activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. 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. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to provide only symptomatic relief of acute as well as chronic pain and inflammation. It has been generally accepted that the inhibition of Cox mediates the anti-inflammatory, antipyretic and analgesic effects of NSAIDs [3], where analgesia has been associated with selective Cox-2 inhibition. The selective inhibition of Cox-2 seemed not to be enough to mediate the anti-nociceptive activity of NSAIDs in several models of acute pain [4]. Newer regimens are needed to reduce the risks of NSAIDs while achieving better analgesic and anti-inflammatory effects
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