The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats

Gaspani, Leda; Bianchi, Mauro; Limiroli, Elena; Panerai, Alberto E.; Sacerdote, Paola

doi:10.1016/s0165-5728(02)00165-0

Cited by 119 publications

(107 citation statements)

References 36 publications

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“…The decrease of IL-2 production in Group 3 treated with 1 mg/kg tramadol was due to insufficient pain relief or immunosuppression mediated via μ-receptor. This was confirmed by several experiments (Sacerdote et al, 1997;1999;Gaspani et al, 2002). It showed that IL-2 and morphine exerted similar effects in various aspects by decreasing intracellular adenosine 3',5'-cyclic phosphate (cAMP) content, modulating neuroendocrine activity, suppressing afferent sensory transmission and serving as Ca 2+ channel blockers (Plata-Salamán and Ffrench-Mullen, 1993;Song et al, 2002a).…”

Section: Modulation Of Cytokine Production By Tramadolmentioning

confidence: 66%

“…First, the decrease of IL-2 production treated with low dose of tramadol may be due to its affinity to μ-receptor, while with higher dose the non-opioid mechanism may play a key role in immunomodulation by tramadol. Second, the effects of tramadol on cytokine production may be mainly attributed to the intrinsic immunomodulatory properties of tramadol taken perioperatively, due to the serotonergic descending inhibitory system, including the increase of the serotonergic tone that has been usually associated with stimulation of lymphocyte proliferation, increase of IL-2 production and decrease of IL-6 production, can help to attenuate postoperative immunosuppression (Sacerdote et al, 1997;1999;Gaspani et al, 2002;Wang et al, 2003). In short, the antinociceptive mechanism of tramadol combined with the opioid and serotonergic system may play an important role in immune responses.…”

Section: Modulation Of Cytokine Production By Tramadolmentioning

confidence: 99%

“…Cytokines play a pivotal role in coordination and regulation of immune responses (Sacerdote et al, 1997;1999;Gaspani et al, 2002;Niemand et al, 2003). Surgical trauma and anesthesia are associated with a complex dysregulation of the immune system and with the activation of both proinflammatory and anti-inflammatory responses (Salo, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain

Liu

Zhu

Wang

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To evaluate the effects of tramadol on the proinflammatory responses in a rat model of incisional pain by investigating its effects on nociceptive thresholds and serum interleukin-6 (IL-6) and IL-2 levels. Methods: Forty-two male Sprague-Dawley (SD) rats scheduled for plantar incision were randomly divided into 7 groups (n=6 in each group). Rats in Group 1 receiving general anesthesia with no incision were served as control; At 30 min before skin incision, Groups 2~5 were given 5 ml normal saline or 1, 10, and 20 mg/kg tramadol, respectively, intraperitoneally (i.p.); Group 6 received 10 mg/kg tramadol after operation; Group 7 received 10 mg/kg tramadol before incision, followed by 200 μg/kg naloxone after operation. Mechanical allodynia was measured by electronic von Frey filament to evaluate the nociceptive thresholds 1 h before incision, and 1 h and 2 h after operation. Serum IL-6 and IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA) 2 h after operation. Results: Mechanical thresholds decreased significantly and serum IL-6 level increased significantly after operation in Group 2 compared with control (P<0.01), and these changes were reversed respectively by tramadol in a dose-dependent manner (P<0.05 and P<0.01, respectively). IL-2 level remained unchanged after operation in Group 2, but decreased in Group 3 (P<0.05), then gradually returned to the normal level in Groups 4 and 5. The intraperitoneally injected tramadol (10 and 20 mg/kg) produced a potent and dose-dependent antinocicptive effect on the lesioned paw. The antinocicptive effects of tramadol were partially antagonized by naloxone (200 μg/kg), suggesting an additional non-opioid mechanism. Conclusion: The results suggest that tramadol could be a good choice for the treatment of pain under the conditions that immunosuppression may be particularly contraindicated.

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Section: Modulation Of Cytokine Production By Tramadolmentioning

confidence: 66%

Section: Modulation Of Cytokine Production By Tramadolmentioning

confidence: 99%

See 1 more Smart Citation

Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain

Liu

Zhu

Wang

et al. 2008

J. Zhejiang Univ. Sci. B

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“…Based on observations that applied in analgesic doses, tramadol and morphine exert different immune responses in both humans and rodents. Concomitant with a reciprocal effect on natural killer cell activity, 19,22,23 it is conceivable that the outcome regarding the engulfing function of the phagocytic cells will proceed through different pathways. Moreover, and in contrast to other opioids, the analgesic action of tramadol is only partially inhibited by the opioid antagonist naloxone, which suggests the existence of another mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

Tramadol does not impair the phagocytic capacity of human peripheral blood cells

Beilin

Grinevich

Yardeni

et al. 2005

Can J Anesth/J Can Anesth

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Purpose:The inhibitory effect of opioids on phagocytic cell capacity is well established. However, the effect of synthetic analgesics on this aspect of cell function is controversial. It was the aim of the study to compare the in vitro effect of tramadol with that of morphine on the engulfing ability of peripheral blood phagocytic cells from healthy volunteers. Methods:Peripheral blood polymorphonuclear cells and monocytes from healthy volunteers were incubated with 5, 10 and 20 µg·mL -1 tramadol, or with 20, 40 and 80 ηg·mL -1 morphine. To each tube, 0.05 mL of 5% suspension of latex beads 0.8 µm in diameter was added. After incubation for 60 min the percentage of cells engulfing latex particles and the phagocytic index (number of particles phagocytized by each individual cell) were detected. Results:Tramadol affected neither the percentage of cells phagocyting latex particles, nor the phagocytic index of both polymorphonuclear cells and monocytes. On the other hand, incubation with 20, 40 and 80 ηg·mL -1 morphine caused 11%, 14% and 24% decrease in phagocytosis (P < 0.01 -P < 0.001). The percentage of monocytes phagocyting latex particles was lower by 16%, 19% and 12% at the three doses tested (P < 0.01 -P < 0.001). The three doses of morphine caused a dose dependent decrease in the monocyte phagocyting index by 20%, 29% and 35.5% respectively (P < 0.05). The polymorphonuclear phagocyting index was not significantly lower following incubation with the drug (P = 0.053). Conclusion:The lack of noxious effect of tramadol on the engulfing capacity of phagocytic cells suggests additional benefit to the relatively safe profile of the drug. 20 %, 29 % et 35,5 % (P < 0,05). L'indice phagocytaire des polynucléaires n'était pas significativement plus bas à la suite de l'incubation avec le médicament (P = 0,053 Objectif : L'effet inhibiteur des opioïdes sur la capacité des cellules phagocytaires est bien établi. Mais l'effet des analgésiques synthé-tiques est controversé. Nous voulions comparer l'effet in vitro du tramadol et de la morphine sur la capacité d'englobage que possèdent les cellules sanguines phagocytaires périphériques prélevées chez des volontaires sains. Méthode

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“…Opioids could potentially be associated with a longer survival due to improvements in pain, as higher pain scores in patients with cancer are associated with a shorter survival [17][18][19][20]. The chronic effects of opioids on survival could include effects on cancer growth which might be mediated by direct effects of opioids on host cells (including angiogenesis or actions on immune cells) or cancer cells (including cancer cell development, apoptosis and metastasis) [21][22][23][24][25], Figure 1. Opioids can inhibit components of both innate and adaptive immunity [21,22,26,27], although a recent systematic review of non-surgical patients with cancer did not find any studies which correlated immune function to clinical outcomes (e.g.…”

Section: Introductionmentioning

confidence: 99%

Is regular systemic opioid analgesia associated with shorter survival in adult patients with cancer? A systematic literature review

Boland

Ziegler

Boland

et al. 2015

Pain

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Opioids are important in the management of pain in patients with cancer. Clinicians and patients are sometimes concerned about the effect of opioids on survival, which might decrease opioid prescription, compliance and symptom control. We wanted to determine whether opioid analgesia was associated with shorter survival in adult patients with cancer. We systematically searched for studies that assessed the effect of regular systemic opioid analgesia on survival. We identified 526 unique records, with 20 articles meeting inclusion criteria. Thirteen end-of-life studies, including 11 very low quality retrospective studies, did not find a consistent association between opioid analgesic treatment and survival, this evidence comes from low quality studies, so should be interpreted with caution. Seven longer-term studies, including 3 randomised controlled trials and 2 prospective studies were included. Six of these studies indicated that opioids were likely to be associated with a shorter survival. None of these studies were powered to assess the effect of opioids on survival as a primary endpoint. In view of this, no definitive conclusions can be made as to whether opioids affect survival in cancer patients. These data suggest that while opioid analgesia does not affect survival at the end of life, in the context of longer-term treatment, higher quality studies, with survival as a primary endpoint, are needed to confirm an independent association between opioid analgesia and shorter survival. An important limitation of research in this field is that the relationship between greater analgesic requirements and shorter survival may be mediated by painful progressive cancer.

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The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats

Cited by 119 publications

References 36 publications

Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain

Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain

Tramadol does not impair the phagocytic capacity of human peripheral blood cells

Is regular systemic opioid analgesia associated with shorter survival in adult patients with cancer? A systematic literature review

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