Chen Wang1, Zhenwei Zheng2

1Department of Anesthesiology, Second Hospital of Xiamen, Xiamen  361021, Guangdong Province, China
2Department of Anesthesiology, Second Affiliated Hospital of Shantou University Medical College, Shantou  515041, Guangdong Province, China

the Scientific Research Program of Xiamen Science and Technology Bureau, No. 3502Z20077074*

Abstract
BACKGROUND: Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons. Cyclooxygenase (COX) is the rate-limiting en-zyme in prostaglandin synthesis, and COX-2 inhibitor is involved in mechanisms of analgesia and anti-inflammation.
OBJECTIVE: To investigate the effects of COX-2 inhibitor on thermal and mechanical hyperalgesia, as well as expression of growth associated protein 43 (GAP-43) and nerve growth factor (NGF) in dorsal root ganglion, in a rat model of neuropathic pain due to chronic constriction injury.
DESIGN, TIME AND SETTING: A randomized, controlled, comparison study that was performed at the Surgical Department and Pathological Laboratory, Second Affiliated Hospital of Shantou Uni-versity Medical College from September 2006 to September 2007. 
MATERIALS: COX-2 inhibitor, lornoxicam, was purchased from Nycomed Pharmaceutical (Austria); rabbit anti-GAP-43, and rabbit anti-NGF polyclonal antibodies were purchased from Boster, Wuhan, China.
METHODS: A total of 50 adult, Wistar rats were randomly assigned to four groups: normal control  (n = 5), model (n = 15), normal saline control (n = 15), and lornoxicam treatment (n = 15). With ex-ception of the control group, the sciatic nerve of all rats was loosely ligated to establish a model of chronic constriction injury. The model rats were divided into three subgroups according to varying post-operative survival periods: 3, 7 and 14 days (n = 5), respectively. Rats in the lornoxicam treatment group were intraperitoneally injected with 1.3 mg/kg lornoxicam every 12 hours throughout the entire experimental procedure. Rats in the normal saline control group were intraperitoneally injected with 1.3 mL/kg saline.
MAIN OUTCOME MEASURES: Immunohistochemistry revealed expression of GAP-43 and NGF in the L5 dorsal root ganglions. Mechanical withdrawal threshold and thermal withdrawal latency were used to observe neurological behavioral changes in rats.
RESULTS: The relative gray values of GAP-43- and NGF-positive neurons in the model group were remarkably increased compared with the normal control rats (P < 0.01), while the relative gray val-ues in the lornoxicam treatment group were significantly less than the model and normal saline control groups (P < 0.01). Mechanical withdrawal threshold and thermal withdrawal latency gradually decreased with increasing injury time in the model, normal saline control, and lornoxicam treatment groups, and were significantly less than the normal control group (P < 0.05). In addition, mechanical withdrawal threshold and thermal withdrawal latency were significantly greater in the lornoxicam treatment group compared with the model and normal saline control groups (P < 0.05).
CONCLUSION: Intraperitoneal injection of the COX-2 inhibitor lornoxicam attenuated mechanical and thermal hyperalgesia induced by sciatic nerve chronic constriction injury and inhibited the in-creased expression of GAP-43 and NGF.

Key Words: growth associated protein; nerve growth factor; neuropathic pain; cyclooxygenase inhibitor; lornoxicam; dorsal root ganglion

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