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Research article
The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation
Mennatallah Gowayed
Pharos University in Alexandria
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8674-8516
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 investigation.
Keywords
Neostigmine, celecoxib, diclofenac, writhing, formalin induced edema
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CURRENT STATUS: Under Revision
Version 2
Posted 11 Aug, 2020
No community comments so far
Editorial decision: Minor revision
On 12 Jan, 2021
Review #1 received
Received 19 Dec, 2020
Reviewer #1 agreed
On 13 Oct, 2020
Reviewers invited
Invitations sent on 12 Oct, 2020
Editor assigned
On 05 Aug, 2020
Submission checks complete
On 04 Aug, 2020
Editor invited
On 04 Aug, 2020
No comments provided
Editorial decision: Major revision
On 27 Jul, 2020
Review #2 received
Received 26 Jul, 2020
Reviewer #2 agreed
On 06 Jul, 2020
Review #1 received
Received 30 May, 2020
Reviewer #1 agreed
On 10 May, 2020
Reviewers invited
Invitations sent on 08 May, 2020
Editor assigned
On 22 Apr, 2020
Submission checks complete
On 21 Apr, 2020
Editor invited
On 21 Apr, 2020
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This preprint is under consideration at BMC Pharmacology and Toxicology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation
Mennatallah Gowayed
Pharos University in Alexandria
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8674-8516
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 2
Posted 11 Aug, 2020
No community comments so far
Editorial decision: Minor revision
On 12 Jan, 2021
Review #1 received
Received 19 Dec, 2020
Reviewer #1 agreed
On 13 Oct, 2020
Reviewers invited
Invitations sent on 12 Oct, 2020
Editor assigned
On 05 Aug, 2020
Submission checks complete
On 04 Aug, 2020
Editor invited
On 04 Aug, 2020
No comments provided
Editorial decision: Major revision
On 27 Jul, 2020
Review #2 received
Received 26 Jul, 2020
Reviewer #2 agreed
On 06 Jul, 2020
Review #1 received
Received 30 May, 2020
Reviewer #1 agreed
On 10 May, 2020
Reviewers invited
Invitations sent on 08 May, 2020
Editor assigned
On 22 Apr, 2020
Submission checks complete
On 21 Apr, 2020
Editor invited
On 21 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 investigation.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8