Effect of nicotine withdrawal on pain sensitivity in rats to mechanical stimulation and thermal stimulation

Z. Liu, X.-W. Liu, S.-F. Lu, A.-L. Yu, Z.-W. Zhang

Department of Anesthesiology, Liaocheng People’s Hospital, Liaocheng, Shandong Province, China. lljhcn@163.com

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• Pharmacology

OBJECTIVE: To establish an improved rat model of nicotine withdrawal and dependence by subcutaneous injection of pure nicotine, and observe the effect of nicotine withdrawal on the pain sensitivity in rats.

MATERIALS AND METHODS: 30 SD rats were randomly divided into 5 groups with 6 rats in each group, including the control group, normal saline group (NS group), nicotine group of 3 mg/kg/d (NT3 group), nicotine group of 9 mg/kg/d (NT9 group) and nicotine group of 18 mg/kg/d (NT18 group). The 5 groups were respectively subcutaneously injected with nothing, normal saline, 1 mg/kg nicotine, 3 mg/kg nicotine and 6 mg/kg nicotine with 3 times per day for 7 consecutive days. 60 min after last injection in the 7th d, 1 mg/kg mecamylamine was subcutaneously injected. The body weight change, survival and nicotine withdrawal score of rats were observed during injection of nicotine and after withdrawal. Mechanical withdrawal threshold (MWT) and Thermal withdrawal latency (TWL) in the right hind sole of another 18 rats selected from the control group, NS group and NT9 group (6 rats from each group) were respectively tested in 7d after injection of normal saline or nicotine.

RESULTS: Compared with the NT3 group, the body weight of rats in the NT9 group and NT18 group were slowly increased in 7d after injection of nicotine (p < 0.05), but were rapidly increased in 1d and 2d after withdrawal (p < 0.01). Rats in the NT9 group and NT18 group had more withdrawal symptoms after stimulation with mecamylamine (p < 0.01), but the mortality of rats in the NT18 group reached 17%. Compared with the control group, MWT in the rats of the NT9 group were significantly decreased in 1-7d after nicotine withdrawal (p < 0.01), and were particularly significantly decreased in 1d and 2d (p < 0.01); TWL was also significantly decreased (p < 0.01), and was most significantly decreased in 4d (p < 0.01).

CONCLUSIONS: An improved rat model of nicotine dependence and withdrawal can be successfully established by intermittent subcutaneous injection of nicotine at 9 mg/kg/d for 7 days, and the pain sensitivity in rats is increased after nicotine withdrawal.

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