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《中国神经再生研究：英文版》
>Effects of cyclooxygenase 2 inhibitor on growth-associated protein 43 and nerve growth factor expression in dorsal root ganglion during neuropathic pain development
Effects of cyclooxygenase 2 inhibitor on growth-associated protein 43 and nerve growth factor expression in dorsal root ganglion during neuropathic pain development
BACKGROUND:Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons.Cyclooxygenase(COX) is the rate-limiting enzyme 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 University 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 exception 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 values 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 increased expression of GAP-43 and NGF.
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