2013•Zhongguo yaolixue tongbaoRequires access
Effect of intrathecal injection of anti-rat IL-18 antibody on the development of morphine tolerance in rats
Weiyan Li
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Abstract
Aim To investigate the effect of blocking interleukin-18 in the spinal cord on the development of morphine tolerance in rats and its possible underlying mechanisms.Methods Forty male Sprague Dawley(SD) rats were randomly divided into 5 groups(n=8): saline control group(group Ⅰ),morphine tolerance group(group Ⅱ),IgG control group(group Ⅲ),anti-rat IL-18 antibody treatment group(group Ⅳ: 0.4 μg and group Ⅴ: 4 μg).Firstly all rats were implanted with intrathecal(i.t.) catheters.Then they were tested to ensure the position of catheters five days after surgery(recorded as the first day).Tolerance to morphine antinociceptive effect was induced and drugs were injected from day 3 to day 9.On day 2 and 10,paw withdrawal thermal latency(PWTL)of the basic and 30 min after morphine injection via tail vein were evaluated in all rats and the percentage of maximal possible antinociceptive effect(%MPE) of 30 min was calculated.Lastly the spinal cord lumbar enlargement was obtained immediately after the behavioral tests on day 10 to determine the expression of ERK and p-ERK by western bolt and the immunoreactivity of GFAP by immunofluorescence.Results ① On day 2 there was no significant difference of the %MPE among five groups(P0.05).On day 10,compared with group I,the %MPE was declined significantly in group Ⅱ-Ⅴ.Compared with group Ⅱ,the %MPE was increased significantly in group Ⅴ(P0.05)while no marked difference in group Ⅲ and Ⅳ(P0.05).② Compared with group I,the expression of p-ERK was increased significantly in group Ⅱ-Ⅴ.Compared with group Ⅱ,the expression of p-ERK was decreased significantly in group Ⅴwhile no marked difference in group Ⅲ and Ⅳ.③ Compared with group Ⅰ,the immunoreactivity of GFAP was markedly increased in group Ⅱ,Ⅲ and Ⅳ.Compared with group Ⅱ,the immunoreactivity was decreased significantly in groupⅤ.Conclusion Anti-rat IL-18 antibody can attenuate the development of morphine tolerance in naive rats through inhibiting the phosphorylation of ERK and activation of astrocytes in the spinal cord.