01701-A: Determining the Effect of Pain Medication on Immune Function: Part 1

Project Summary

Introduction: Opioids are often used to treat pain in many situations, including during the post-operative period and often in dogs with a high risk for infection. In addition to providing excellent pain control, opioids directly modulate the immune system. In other species, certain opioids suppress the beneficial aspects (e.g., phagocytosis and microbial killing) while promoting detrimental aspects (e.g., excessive cytokine production) of the immune response to infection while other opioids have little effect. Thus, the selection of intra-and post-operative opioids could affect the incidence of post-operative infection in dogs. Despite extensive work in other species supporting the profound immunologic effects of opioids, to date there is no published information pertaining to the effects of opioids on immune function in dogs. The objective of this study is to compare the effects of the 3 most commonly used opioids in dogs (morphine, fentanyl and buprenorphine) on phagocytic function and cytokine production in dogs. Since hundreds of thousands of dogs undergo surgery or suffer trauma necessitating administration of opioids every year, and postoperative infection rate in dogs have been reported as high as 27%, the results of this study could have a dramatic and widespread impact on canine health. Materials and Methods: With informed owner consent, blood samples were collected from healthy pet dogs. Blood was incubated with morphine, buprenorphine, fentanyl or a saline control. Following incubation, two different assays were performed to measure the ability of canine neutrophils in blood to engulf bacteria (phagocytosis) and kill engulfed bacteria (respiratory burst). In addition, blood was cultured with parts of bacteria called pathogen associated molecular patterns to determine the ability of white blood cells to respond to this threat via production of pro-inflammatory TNF and anti-inflammatory IL-10. Results and conclusions: We found that the opioids tested did not alter phagocytosis (engulfing) of bacteria but that Morphine altered bacterial killing mechanisms. Additionally, certain opioids alter production of cytokines. While this is an initial in vitro investigation, there could be clinical implications of our findings in dogs. Pro-inflammatory shifting may put dogs treated with morphine at risk for inflammation induced complications, especially after surgery. We plan to investigate this further by first assessing the effects of morphine in dogs in vivo and in dogs with inflammatory conditions and then by evaluating clinical outcomes in dogs managed with morphine compared to other opioids.

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