Morphine Reduces Local Cytokine Expression and Neutrophil Infiltration after Incision

Clark, J. David; Shi, Xiaoshuang; Li, Xiangqi; Qiao, Yanli; Liang, De‐Yong; Angst, Martin S.; Yeomans, David C.

doi:10.1186/1744-8069-3-28

Cited by 108 publications

(117 citation statements)

References 47 publications

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“…Many studies have indicated that opioids are effective for the treatment of postoperative pain and that incisional pain has been classified as opioid sensitive (St A Stewart and Martin, 2003;Whiteside et al, 2004;Clark et al, 2007). In the present study, we found that the effect of tramadol was not completely blocked by 200 μg/kg opioid antagonist naloxone, suggesting that tramadol-induced antinociception may be partially mediated via opioid receptors.…”

Section: Evaluation Of the Opioid Component Of Tramadol On The Presensupporting

confidence: 60%

“…Opioid analgesics are commonly used for the treatment of both acute (e.g., post-operative) and chronic pain, but some studies argued that they also cause suppression to immune system (Manfredi et al, 1993;Clark et al, 2007). Tramadol hydrochloride is a centrally acting analgesic with opioid and non-opioid like properties (Raffa et al, 1992;Kayser et al, 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: Evaluation Of the Opioid Component Of Tramadol On The Presensupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

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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“…However, several studies, 50 -52 including ours (unpublished observation), clearly demonstrate the surface expression of mu opioid receptors on keratinocytes. Also, a recent report by Clark et al 48 shows significant inhibition of early KC expression from wound edge keratinocytes following acute morphine treatment. These studies implicate keratinocytes as the potential source of KC synthesis in our model of wound healing and morphine modulation of KC synthesis may be mediated through mu opioid receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in support of wounding as a potent stimulus for KC secretion is provided by several recent reports. 48,49 These studies identify wound edge keratinocytes as an important source of cytokines in the acute phase following wounding and KC as the predominant chemokine present at enhanced levels at wound sites following incision. Although our studies show significant decrease in the early expression of KC following morphine treatment, the cell type responsible for KC expression was not identified.…”

Section: Discussionmentioning

confidence: 99%

Chronic Morphine Administration Delays Wound Healing by Inhibiting Immune Cell Recruitment to the Wound Site

Martin

Koodie

Krishnan

et al. 2010

The American Journal of Pathology

107

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Patients prescribed morphine for the management of chronic pain , and chronic heroin abusers , often present with complications such as increased susceptibility to opportunistic infections and inadequate healing of wounds. We investigated the effect of morphine on wound-healing events in the presence of an infection in an in vivo murine model that mimics the clinical manifestations seen in opioid user and abuser populations. We show for the first time that in the presence of an inflammatory inducer, lipopolysaccharide, chronic morphine treatment results in a marked decrease in wound closure, compromised wound integrity, and increased bacterial sepsis. Morphine treatment resulted in a significant delay and reduction in both neutrophil and macrophage recruitment to the wound site. The delay and reduction in neutrophil reduction was attributed to altered early expression of keratinocyte derived cytokine and was independent of macrophage inflammatory protein 2 expression, whereas suppression of macrophage infiltration was attributed to suppressed levels of the potent macrophage chemoattractant monocyte chemotactic protein-1. When the effects of chronic morphine on later wound healing events were investigated, a significant suppression in angiogenesis and myofibroblast recruitment were observed in animals that received chronic morphine administration. Taken

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“…In order to explain the histological differences, we evaluated the immunological background of the lesions. Recent studies have demonstrated that stimulated keratinocytes can secrete neuropeptides, such as substance P (SP), and pro-inflammatory cytokines like IL-1α, IL-1β, IL-6 and TNF-α 8,9 . In addition, extravasated mucus can induce extensive macrophage reactions 10 .…”

Section: Discussionmentioning

confidence: 99%

Clinical and Immunohistochemical Characteristics of Mucoceles

2009

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Background: Mucoceles have diverse clinical and histological features. Their pathogenesis remains to be elucidated. Objective: To determine the structural and/or pathogenic differences between two clinically different types of mucoceles. Methods: Seventeen oral mucoceles were examined clinically and immunohistologically. The mucoceles were divided into two groups by their clinical manifestations: papular group (PG) and nodular group (NG). Results: Histologically, granulation tissue formed more frequently in the NG group, while CD4 and CD8 positive cells were more abundant in the PG group. There were no significant differences in the tumor necrosis factor-alpha or the matrix metalloproteinases (MMP)-2 and 9, between the two groups. Conclusion: There were significant differences in the depth of the lesions, granulation tissue formation and infiltrating T lymphocytes between the PG and NP type of mucoceles. These findings suggest that the clinical manifestations may be influenced by the type of inflammatory response and extracellular matrix remodeling. (Ann Dermatol 21(4) 345∼

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Morphine Reduces Local Cytokine Expression and Neutrophil Infiltration after Incision

Cited by 108 publications

References 47 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

Chronic Morphine Administration Delays Wound Healing by Inhibiting Immune Cell Recruitment to the Wound Site

Clinical and Immunohistochemical Characteristics of Mucoceles

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