Background and objective: There is increasing evidence that the nervous system is in two-way interaction with the immune system. To study the relationship between the opioid and immune systems, the anti-inflammatory effect of naloxone - an opioid receptor antagonist - in the air pouch model as an animal model of rheumatoid arthritis was studied.
Methods: Sterile air (20 and 10 ml) was subcutaneously injected into the back of the animals on days 1 and 3, respectively. On the 6th day, carrageenan was injected into the pouch. Normal saline and different doses of naloxone were injected immediately, as well as 24 and 48 hours after carrageenan in the control and treatment groups, respectively. After 72 hours, granulation tissue was opened, the pouch fluid was collected to determine the volume of exudates, the concentration of Vascular Endothelial Growth Factor (VEGF) and Interleukin 1 beta (IL-1β) and count of leukocyte. Granulation tissue was extruded and weighed. To assay the angiogenesis, the granulation tissue was homogenized and centrifuged, and the supernatant was filtered by a 0.22µ filter. Hemoglobin concentration was determined by the hemoglobin kit.
Results: Naloxone clearly reduced leukocyte accumulation (p<0.01), exudate volume (p<0.001), granulation tissue weight (p<0.01), and amount of angiogenesis in the granulation tissue (p<0.001). In addition, VEGF and IL-1β levels were decreased significantly (p<0.01) and (p<0.001), respectively. 
Conclusion: Naloxone can reduce inflammatory and angiogenesis parameters in an air pouch inflammatory model. The anti-inflammatory effect is probably related to inhibition of leukocyte accumulation due to decreased concentration of inflammatory cytokines in exudates.
Keywords: Naloxone, Inflammation, Angiogenesis, Vascular Endothelial Growth Factor, Interleukin-1


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