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Morphine attenuates leukocyte/endothelial interactions
X Ni1, K R Gritman, T K Eisenstein
1Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania, 19140, USA.
Abstract:
Gram-negative sepsis and subsequent endotoxic shock after surgery remain problematic in the United States and throughout the world. While morphine is widely prescribed for postoperative trauma pain management, there are reports that morphine may compromise the immune system and contribute to postoperative sepsis. The current study tested the hypothesis that morphine attenuates leukocyte rolling and sticking in both arterioles and venules via nitric oxide production. Nude mice implanted with slow-release morphine pellets were used in this study. The dorsal skinfold chamber model for intravital fluorescence microscopy on awake mice was used. Leukocyte/endothelial interactions were evaluated after bolus injection of oxidized low density lipoprotein. Morphine was found to significantly attenuate leukocyte rolling and sticking in both the arterial and venular side of the microcirculation. This attenuation was reversed by simultaneous implantation of naloxone pellets. The mechanisms of this attenuation were further investigated by administration of the nitric oxide synthase inhibitors NG-nitro-l-arginine (NOLA) and aminoguanidine (AG) in drinking water. NOLA was found to significantly reverse this morphine-induced attenuation of leukocyte rolling and sticking in both arterioles and venules. However, AG did not have the same effect. The results indicate that morphine interferes with leukocyte/endothelial cell interactions via stimulation of nitric oxide production.
Insights
Morphine use may reduce immune cell sticking during sepsis, potentially by increasing nitric oxide (NO) production. This effect was blocked by naloxone and a specific NO inhibitor, suggesting a role for NO in morphine
Area of Science:
- Immunology
- Pharmacology
- Microcirculation Research
Background:
- Gram-negative sepsis and endotoxic shock post-surgery are significant global health issues.
- Morphine, a common postoperative pain reliever, is suspected to impair immune function and increase sepsis risk.
- Understanding morphine's impact on leukocyte behavior is crucial for managing postoperative complications.
Purpose of the Study:
- To investigate whether morphine attenuates leukocyte rolling and sticking in microcirculation.
- To determine if this effect is mediated by nitric oxide (NO) production.
- To explore the role of opioid receptors in morphine's effects on leukocyte-endothelial interactions.
Main Methods:
- Utilized a dorsal skinfold chamber model in nude mice for intravital fluorescence microscopy.
- Administered slow-release morphine pellets and evaluated leukocyte/endothelial interactions after oxidized low-density lipoprotein injection.
- Investigated the role of nitric oxide synthase (NOS) inhibition using NG-nitro-l-arginine (NOLA) and aminoguanidine (AG).
Main Results:
- Morphine significantly reduced leukocyte rolling and sticking in both arterioles and venules.
- Naloxone pellets reversed the attenuating effects of morphine.
- NO synthase inhibition with NOLA, but not AG, reversed the morphine-induced attenuation.
Conclusions:
- Morphine interferes with leukocyte/endothelial cell interactions.
- This interference appears to be mediated through the stimulation of nitric oxide production.
- The findings suggest a potential mechanism by which morphine might influence inflammatory responses in sepsis.