COX-2 dependent inflammation increases spinal Fos expression during rodent postoperative ileus

Area of Science:

• Neuroscience
• Gastroenterology
• Inflammation Research

Background:

• Postoperative ileus is a common complication following abdominal surgery.
• Cyclooxygenase 2 (COX-2) and prostaglandins (PGs) are implicated in the inflammatory processes contributing to ileus.
• The role of COX-2 as a neuronal modulator in primary afferent activation during ileus requires further elucidation.

Purpose of the Study:

• To investigate the role of COX-2 in primary afferent activation during postoperative ileus.
• To utilize spinal Fos expression as a marker for primary afferent activation.
• To assess the impact of COX-2 inhibition on ileus-related parameters.

Main Methods:

• Intestinal manipulation was performed on rats, COX-2(+/+) mice, and COX-2(-/-) mice.
• Fos immunoreactivity (IR) in the spinal cord, muscularis circumference, and leucocytic infiltrate were measured.
• Prostaglandin E2 (PGE2) levels were quantified, and COX-2 was inhibited pharmacologically (DFU) and genetically.

Main Results:

• Postoperative intestinal manipulation significantly increased spinal Fos IR, indicating primary afferent activation.
• Ileus, characterized by increased muscularis circumference and leucocytic infiltrate, was observed.
• Both pharmacological COX-2 inhibition (DFU) and genetic absence of COX-2 (COX-2(-/-) mice) attenuated Fos IR and reduced ileus parameters.
• PGE2 levels were elevated postoperatively and normalized with DFU treatment.

Conclusions:

• COX-2 plays a critical role in the prolonged primary afferent activation following small bowel manipulation.
• This COX-2-mediated activation contributes to the development of postoperative ileus.
• Targeting COX-2 may offer a therapeutic strategy for managing postoperative ileus.