While this study presents valuable insights into the dose-dependent effects of Palmitoylethanolamide (PEA) on brain function and lipid signaling, the observed inverse relationship between PEA dose and negative BOLD signal requires further explanation. Specifically, could the authors explain why the lowest dose (3 mg/kg) results in the most significant reduction in BOLD signal, while higher doses show increased connectivity and activity? This mechanism needs a clearer interpretation.
Additionally, while the study assesses nociception via the tail flick test, it does not discuss how these behavioral changes relate to the brain activity observed. Clarification on how pain-related brain regions are impacted by PEA would strengthen the connection between behavior and neuroimaging. Could the authors please clarify this too?
Lastly, the exclusion of rats due to motion artifacts raises potential concerns about the representativeness of the remaining sample. I would appreciate the authors` thoughts on this as well.