Preemptive analgesic effects of low-dose ketamine on growth-associated protein expression in dorsal root ganglion of chronic constriction injury model rats

Shuyong Lin; Chen Wang

摘要：BACKGROUND: Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists and plays an important role in the treatment of pain.OBJECTIVE: To analyze the preemptive analgesic effects of different doses of ketamine on growth-associated protein-43 (GAP-43) expression in dorsal root ganglion in a rat model of chronic sciatic nerve constricted injury, and to study the differences between high-dose and low-dose ketamineDESIGN: Randomized controlled animal study.SETTING: Medical College of Shantou University. MATERIALS: Thirty-five adult male Sprague Dawley rats were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. Ketamine hydrochloride injection was provided by Hengrui Pharmaceutical Co., Ltd., Jiangsu. METHODS: This study was performed at the Immunological Laboratory, Medical College of Shantou University from September to December 2006. Model of chronic sciatic nerve constricted injury: after anesthesia, the right sciatic nerve was exposed and ligated 1-cm distal to the ischiadic tuberosity with a No. 3-0 cat gut suture. Grouping and intervention: 35 rats were randomly divided into 4 groups: normal control group (n = 5), chronic constriction injury (CCI) group (n = 10), low-dose ketamine group (n = 10), and high-dose ketamine group (n = 10). Rats in the normal control group did not undergo any surgery or drug intervention. Rats in the CCI group received intraperitoneal injection of saline (1 mL), and their sciatic nerves were ligated after 10 minutes. Rats in the low-dose ketamine group underwent intraperitoneal injection of ketamine (25 mg/kg) 10 minutes prior to ligation of sciatic nerve; while, rats in the high-dose ketamine group were given intraperitoneal injection of ketamine (50 mg/kg) 10 minutes prior to ligation of sciatic nerve. On the third and the seventh days after surgery, dorsal root ganglion were resected from the sciatic nerve and cut into sections. MAIN OUTCOME MEASURES: GAP-43 expression in dorsal root ganglion was detected by immunohistochemistry and image analysis system, as well as semi-quantitative analysis.RESULTS: Thirty-five Sprague Dawley rats were included in the final analysis. Qualitative analysis: GAP-43 expression in the CCI group was higher than in the normal control group. Quantitative analysis: after three post-operative days, GAP-43 expression in the CCI group was significantly higher than in the normal control group (t = 22.919, 7.319, P < 0.05). GAP-43 expression in the low-dose and high-dose ketamine group was significantly lower than in the CCI group (t = 11.166, 26.474, P < 0.05). After seven postoperative days, GAP-43 expression in the low-dose and high-dose ketamine groups was significantly lower than in the CCI group (t = 2.382, 5.016, P < 0.05). CONCLUSION: Preoperative administration of ketamine inhibited the increased GAP-43 expression in dorsal root ganglion during neuropathic pain.