High-dose naproxen aggravates pancreatic fibrosis in a rat model of chronic pancreatitis.
OBJECTIVE
: 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 alpha concentration were studied, and immunohistochemical analysis of alpha-smooth muscle actin in the pancreas was performed.


RESULTS
Pancreatic collagen content and alpha-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.
Zhang
Wei
W
Division of Field Medicine, Department of Internal Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Gao
Jun
J
Zhao
Tao
T
Wu
Wenbin
W
Bai
Yu
Y
Zou
Duowu
D
Li
Zhaoshen
Z
D000199:Actins / Q000032:analysis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D005355:Fibrosis; D008297:Male; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D050500:Pancreatitis, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha; C498862:Acta2 protein, rat