Bakr et al Clin J Pain Volume 00, Number 00, ’’ 2016
6 | www.clinicalpain.com Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. was a significant decrease in CD4, CD8, and CD56 in group
M, compared with groups T and K and in CD3, CD8, and
CD56 in group T compared with group K at 90 minutes postoperatively. After 24 hours, there was a decrease in
CD4, and CD8 in group M in comparison to group T.
Furthermore, there was a decrease in CD4 and CD56 in groupsMand T in comparison to group K. So T group had less inhibitory effects on immune functions than M group, and ketorolac had the least immunosuppressive effect among the 3 drugs. Lower immunosuppressive effect of tramadol compared with morphine could be explained by its weaker opioid agonistic effect on m-receptors and by its nonopioid mechanism of action where it acts by inhibition of neuronal uptake of noradrenaline and serotonin. Agreeing with our findings, Sacerdote et al5 studied the effects of tramadol and morphine on immune responses and pain postoperatively in cancer patients. They concluded that immediately postoperatively T-lymphocyte proliferation was significantly lower than basal proliferative levels in the 2 groups, lymphocyte proliferation in tramadol group returned to its baseline and NK activity showed a significant increase 2 hours after tramadol administration. Zhou et al7 concluded that tramadol can reduce the decrease of T-lymphocytes subsets and NK cells, thus improve the cellular immune function in the perioperative period of gastric cancer surgery. Ketorolac had the least immunosuppressive effect in this study; this is consistent with the results obtained in previous studies that investigated the influence of NSAIDs on antitumor immunity. These studies identified the role of PGs in immunity and inflammation26,27 and the positive effect of NSAIDs on immunity and against cancer progression in both animals and humans.28–32 Indeed, cyclooxygenase- 2 (COX-2) inhibitors are active in some models of breast cancer, and COX-2 could play a role in tumor development.31 In fact, overexpression of COX-2 in breast cancer leads to stimulation of epithelial cell proliferation, inhibition of apoptosis, stimulation of angiogenesis, immune suppression, and increases the production of mutagens.30 This favors breast tumor growth and increases the risk of cancer relapse. These effects are mostly mediated by PGs and specifically PGE2.26,31 PGE2 is released by monocytes and dendritic cells to regulate the inflammatory cascade …show more content…
Changes in CD8 Percentage in the 3 Studied Groups
Mean±SE
CD8 Group M (n=20) Group T (n=20) Group K (n=20) P1 P2 P3
Baseline 20.95±2.87 22.00±3.11 22.78±3.06 0.478 0.227 0.606
After 90 min 6.62±1.89 15.62±2.92 18.44±1.91 0.000* 0.000* 0.042*
After 24 h 6.56±1.72 9.46±1.50 9.65±3.78 0.048* 0.093 0.709
P4 0.001* 0.033* 0.001*
P5 0.001* 0.002* 0.001*
Baseline (immediately postoperative preanalgesic).
After 90 minutes and 24 hours (postoperative postanalgesic).
Data expressed as (mean±SE).
P1: comparison between group M and group T.
P2: comparison between group M and group K.
P3: comparison between group T and group K.
P4: comparison between baseline and after 90 minutes.
P5: comparison between baseline and after 24 hours.
*Significant P-value.
Group K indicates ketorolac; group M, morphine; group T, tramadol.
FIGURE 8. Changes in CD8 percentage in the 3 studied groups.
Group M: morphine; group T: tramadol; group K: ketorolac.
Baseline (immediately postoperative preanalgesic). After
90 minutes and 24 hours (postoperative postanalgesic). *, Statistically significant difference in comparison with baseline. ?,
Statistically significant difference between each 2 groups at
90 minutes.K, Statistically significant difference between M
6 | www.clinicalpain.com Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. was a significant decrease in CD4, CD8, and CD56 in group
M, compared with groups T and K and in CD3, CD8, and
CD56 in group T compared with group K at 90 minutes postoperatively. After 24 hours, there was a decrease in
CD4, and CD8 in group M in comparison to group T.
Furthermore, there was a decrease in CD4 and CD56 in groupsMand T in comparison to group K. So T group had less inhibitory effects on immune functions than M group, and ketorolac had the least immunosuppressive effect among the 3 drugs. Lower immunosuppressive effect of tramadol compared with morphine could be explained by its weaker opioid agonistic effect on m-receptors and by its nonopioid mechanism of action where it acts by inhibition of neuronal uptake of noradrenaline and serotonin. Agreeing with our findings, Sacerdote et al5 studied the effects of tramadol and morphine on immune responses and pain postoperatively in cancer patients. They concluded that immediately postoperatively T-lymphocyte proliferation was significantly lower than basal proliferative levels in the 2 groups, lymphocyte proliferation in tramadol group returned to its baseline and NK activity showed a significant increase 2 hours after tramadol administration. Zhou et al7 concluded that tramadol can reduce the decrease of T-lymphocytes subsets and NK cells, thus improve the cellular immune function in the perioperative period of gastric cancer surgery. Ketorolac had the least immunosuppressive effect in this study; this is consistent with the results obtained in previous studies that investigated the influence of NSAIDs on antitumor immunity. These studies identified the role of PGs in immunity and inflammation26,27 and the positive effect of NSAIDs on immunity and against cancer progression in both animals and humans.28–32 Indeed, cyclooxygenase- 2 (COX-2) inhibitors are active in some models of breast cancer, and COX-2 could play a role in tumor development.31 In fact, overexpression of COX-2 in breast cancer leads to stimulation of epithelial cell proliferation, inhibition of apoptosis, stimulation of angiogenesis, immune suppression, and increases the production of mutagens.30 This favors breast tumor growth and increases the risk of cancer relapse. These effects are mostly mediated by PGs and specifically PGE2.26,31 PGE2 is released by monocytes and dendritic cells to regulate the inflammatory cascade …show more content…
Changes in CD8 Percentage in the 3 Studied Groups
Mean±SE
CD8 Group M (n=20) Group T (n=20) Group K (n=20) P1 P2 P3
Baseline 20.95±2.87 22.00±3.11 22.78±3.06 0.478 0.227 0.606
After 90 min 6.62±1.89 15.62±2.92 18.44±1.91 0.000* 0.000* 0.042*
After 24 h 6.56±1.72 9.46±1.50 9.65±3.78 0.048* 0.093 0.709
P4 0.001* 0.033* 0.001*
P5 0.001* 0.002* 0.001*
Baseline (immediately postoperative preanalgesic).
After 90 minutes and 24 hours (postoperative postanalgesic).
Data expressed as (mean±SE).
P1: comparison between group M and group T.
P2: comparison between group M and group K.
P3: comparison between group T and group K.
P4: comparison between baseline and after 90 minutes.
P5: comparison between baseline and after 24 hours.
*Significant P-value.
Group K indicates ketorolac; group M, morphine; group T, tramadol.
FIGURE 8. Changes in CD8 percentage in the 3 studied groups.
Group M: morphine; group T: tramadol; group K: ketorolac.
Baseline (immediately postoperative preanalgesic). After
90 minutes and 24 hours (postoperative postanalgesic). *, Statistically significant difference in comparison with baseline. ?,
Statistically significant difference between each 2 groups at
90 minutes.K, Statistically significant difference between M