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High-Dose Naproxen Aggravates Pancreatic Fibrosis in a Rat Model of Chronic Pancreatitis

Zhang, Wei MD*; Gao, Jun MD, PhD*†; Zhao, Tao MD*; Wu, Wenbin*; Bai, Yu MD; Zou, Duowu MD, PhD*†; Li, Zhaoshen MD, PhD*†

doi: 10.1097/MPA.0b013e3181bb90b5
Original Articles

Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of pain in chronic pancreatitis (CP). This study aimed to investigate the effect of NSAIDs on the inflammation and fibrosis progression in trinitrobenzene sulfonic acid-induced CP rats.

Methods: Chronic pancreatitis was induced by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Naproxen treatment (20 and 40 mg/kg per os [PO] and intraperitoneally) started 2 weeks after the induction of CP for 3 weeks. Histological analysis of the pancreas, Van Gieson staining, and contents of hydroxyproline were used to evaluate pancreatic damage and fibrosis. Furthermore, the effect of naproxen on nociceptive reflective behaviors and serum tumor necrosis factor α concentration were studied, and immunohistochemical analysis of α-smooth muscle actin in the pancreas was performed.

Results: Pancreatic collagen content and α-smooth muscle actin expression were higher in the CP group treated with high-dose (40 mg/kg PO) naproxen (P < 0.05). High-dose naproxen administered orally aggravated pancreatic fibrosis and inflammation (P < 0.05). Instead of playing an analgesic role, high-dose naproxen decreased the thermal withdrawal latencies in CP rats (P < 0.05).

Conclusions: High-dose naproxen treatment (40 mg/kg PO) aggravated pancreatic fibrosis in CP rats and played an algogenic role that suggests the potential risk of long-term use of NSAIDs as analgesic in clinical practice with CP.

From the Divisions of *Field Medicine, and †Gastroenterology, Department of Internal Medicine, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.

Received for publication March 28, 2009; accepted August 5, 2009.

Reprints: Zhaoshen Li, MD, PhD, Division of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China (e-mail:

W. Zhang and J. Gao contributed equally to this work.

This study is supported by the National Natural Science Foundation of China No. 30871157.

© 2010 Lippincott Williams & Wilkins, Inc.