Cincinnati Children’s Hospital Study Addresses How Early Life Surgery Can Influence Later Responses to Pain What are the main findings?

Response: We found that immature macrophages were both necessary and sufficient to regulate prolonged pain-like responses in animal models of post-surgical pain.  Developing macrophages were also necessary for appropriate sensory neuron responses to peripheral stimuli after repeated incision injury.  Surprisingly, we found that these cells underwent a prolonged change in their DNA structure that influenced how specific genes were expressed over time.  One particular gene that was found to be modified after early life surgery was the p75 neurotrophic factor receptor which is known to regulate sensory neuron development and macrophage function.  Deletion of this receptor from both mouse and human macrophages was able to alter behavioral responses to repeated surgeries and the way sensory neurons responded to simulation. 

         We further found that the stem cells in the bone marrow that generate macrophages (among other immune cells) showed an exaggerated pro-inflammatory response to activation if they were derived from animals that underwent early life surgery.  If bone marrow isolated from an animal that experienced neonatal surgery was transplanted into a naïve host, females in particular showed an altered response to surgery. What should readers take away from your report?

Response:      These data suggest that developing macrophages can generate a cellular “memory” of early life injury that influences how they modulate pain-like responses later in life.  This memory appears to be long lasting in both males and females, but females in particular appear to retain this memory for substantially longer time periods.  These and future results could uncover new ways to treat chronic post-surgical pain in children. What recommendations do you have for future research as a result of this study?

Response:      Future research should include studies that investigate whether other cells, including neurons, can develop “memories” of early life injury to subsequently influence pain responses in adolescence and young adulthood.  It is also important to consider sex as a biological variable in any studies looking at the transition from acute to chronic pain after surgery in children. Is there anything else you would like to add? Any disclosures?

Response:      Although more studies are needed to determine if targeting immune memories are a viable strategy to mitigate post-surgical pain in children, it is important to consider that just changing pain medications may not necessarily benefit certain patients that underwent surgery. Finding new targeted therapies for boys and girls that undergo neonatal surgery will be important future endeavors.

Citation: Dourson, A.J., Fadaka, A.O., Warshak, A.M., Paranjpe, A., Weinhaus, B., Queme, L.F., Hofmann, M.C., Evans, H.M., Donmez, O., Forney, C., Weirauch, M.T., Kottyan, L.C., Lucas, D., Deepe Jr., G.S., Jankowski, M.P. 2024. Macrophage memories of early-life injury drive neonatal nociceptive priming. Cell Rep. 43: 114129.

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Last Updated on April 24, 2024 by