McIlwrath SL, Starr ME, High AE, Saito H, Westlund KN. Effect of acetyl-L-carnitine on hypersensitivity in acute recurrent caerulein-induced pancreatitis and microglial activation along the brain’s pain circuitry. World J Gastroenterol 2021; 27(9): 794-814 [PMID: 33727771 DOI: 10.3748/wjg.v27.i9.794]
Corresponding Author of This Article
Sabrina L McIlwrath, PhD, Senior Scientist, Research Service, New Mexico Veterans Affairs Healthcare System, 1501 San Pedro SE, Albuquerque, NM 87108, United States. sabrina.mcilwrath@va.gov
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
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McIlwrath SL, Starr ME, High AE, Saito H, Westlund KN. Effect of acetyl-L-carnitine on hypersensitivity in acute recurrent caerulein-induced pancreatitis and microglial activation along the brain’s pain circuitry. World J Gastroenterol 2021; 27(9): 794-814 [PMID: 33727771 DOI: 10.3748/wjg.v27.i9.794]
World J Gastroenterol. Mar 7, 2021; 27(9): 794-814 Published online Mar 7, 2021. doi: 10.3748/wjg.v27.i9.794
Effect of acetyl-L-carnitine on hypersensitivity in acute recurrent caerulein-induced pancreatitis and microglial activation along the brain’s pain circuitry
Sabrina L McIlwrath, Marlene E Starr, Abigail E High, Hiroshi Saito, Karin N Westlund
Sabrina L McIlwrath, Karin N Westlund, Research Service, New Mexico Veterans Affairs Healthcare System, Albuquerque, NM 87108, United States
Marlene E Starr, Hiroshi Saito, Department of Surgery, University of Kentucky, Lexington, KY 40536, United States
Abigail E High, College of Liberal Arts, University of Texas, Austin, TX 78712, United States
Karin N Westlund, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, United States
Author contributions: McIlwrath SL performed the animal experiments, data analysis, produced the figures, wrote the manuscript; Starr ME assisted with animal caerulein dosing and read the manuscript; High AE analyzed the microglial morphology in the brain sections; Saito H designed the study, read and edited this manuscript; Westlund KN designed the study, read and edited this manuscript; all authors discussed the results, commented on the manuscript, and approved the final version of the article.
Supported byUnited States Department of Veterans Affairs, VA Merit Grant, No. BX002695; and United States National Institute of Health, No. R01AG055359, No. R01GM126181 and No. R01NS39041-15.
Institutional animal care and use committee statement: This study was reviewed and approved by the Institutional Animal Care and Use Committee of the University of Kentucky (IACUC Protocol No. 2010-0736). The animal care facility of the University of Kentucky is accredited by AALAC.
Conflict-of-interest statement: The authors have nothing to disclose. This communication does not necessarily reflect the views of the Department of Veterans Affairs or the United States government.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Corresponding author: Sabrina L McIlwrath, PhD, Senior Scientist, Research Service, New Mexico Veterans Affairs Healthcare System, 1501 San Pedro SE, Albuquerque, NM 87108, United States. sabrina.mcilwrath@va.gov
Received: September 11, 2020 Peer-review started: September 11, 2020 First decision: November 25, 2020 Revised: December 8, 2020 Accepted: January 15, 2021 Article in press: January 15, 2021 Published online: March 7, 2021 Processing time: 172 Days and 11.8 Hours
Core Tip
Core Tip: The caerulein- (CAE) induced pancreatitis model requiring 6 wk of repeated injections is a model of recurrent acute bouts of pancreatitis that causes pancreatic tissue damage and fibrosis. Control repeated i.p. saline injections alone caused abdominal wall injury and hindpaw secondary mechanical hypersensitivity. Treatment with acetyl-L-carnitine significantly attenuated CAE-induced hypersensitivity without alleviating pancreatic histological disruption. Mice with CAE-induced pancreatitis with secondary mechanical and heat hypersensitivity had elevated plus maze anxiety-like behavior. Post-mortem analysis revealed microglial morphology changes indicative of activation in amygdala, hippocampus, hypothalamus, and thalamus, but not in primary somatosensory cortex. These data suggest that activated microglia in these brain regions contribute to chronic hypersensitivity and anxiety-like behaviors in mice with CAE-induced pancreatitis.
