The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation
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
This is a list of supplementary files associated with this preprint. Click to download.
Posted 11 Aug, 2020
On 12 Jan, 2021
Received 19 Dec, 2020
On 13 Oct, 2020
Invitations sent on 12 Oct, 2020
On 05 Aug, 2020
On 04 Aug, 2020
On 04 Aug, 2020
On 27 Jul, 2020
Received 26 Jul, 2020
On 06 Jul, 2020
Received 30 May, 2020
On 10 May, 2020
Invitations sent on 08 May, 2020
On 22 Apr, 2020
On 21 Apr, 2020
On 21 Apr, 2020
The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation
Posted 11 Aug, 2020
On 12 Jan, 2021
Received 19 Dec, 2020
On 13 Oct, 2020
Invitations sent on 12 Oct, 2020
On 05 Aug, 2020
On 04 Aug, 2020
On 04 Aug, 2020
On 27 Jul, 2020
Received 26 Jul, 2020
On 06 Jul, 2020
Received 30 May, 2020
On 10 May, 2020
Invitations sent on 08 May, 2020
On 22 Apr, 2020
On 21 Apr, 2020
On 21 Apr, 2020
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