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KMID : 0356920100590010039
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Korean Journal of Anesthesiology
2010 Volume.59 No. 1 p.39 ~ p.44
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The interaction of intrathecal neostigmine and N6-cyclohexyladenosine on anti-allodynic effects in rats with a nerve ligation injury
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Choi Dae-Kee
Choi Seong-Soo
Hwang Jai-Hyun
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Abstract
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Background: Nerve ligation injury in rats produces a pain syndrome that includes mechanical allodynia. Intrathecal administration of cholinesterase inhibitors or adenosine receptor agonists have anti-allodynic effects in this model. Therefore, we tested the interaction between intrathecal neostigmine and N6-cyclohexyladenosine (CHA) in a rat behavioral model of neuropathic pain.
Methods: Male Sprague-Dawley rats were prepared with tight ligation of the spinal nerves for producing allodynia and with a lumbar intrathecal catheter for drug administration. Allodynia thresholds for hindpaw withdrawal against mechanical stimuli were assessed and converted to percent maximal possible effect. Neostigmine (0.3-10 μg) and CHA (0.03-3 μg) were administered to obtain the dose-response curves and the 50% effective dose (ED50). Equal fractions (1/2, 1/4 and 1/8 ED50s) of the two drugs were administered to establish the ED50 of neostigmine-CHA combination. Side effects were also assessed. The drug interaction was evaluated by isobolographic and fractional analyses.
Results: Neostigmine, CHA, and the neostigmine-CHA combination dose-dependently produced anti-allodynia effects. Side effects such as sedation and motor weakness were similar in the three groups. In the isobolographic analysis, the experimental ED50 for the combination of neostigmine-CHA lay far below and to the left of the theoretical additive line. Fractional analysis indicated that the total combination fraction of the two drugs was 0.39.
Conclusions: Intrathecal co-administration of neostigmine and CHA showed a synergistic anti-allodynia effect.
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KEYWORD
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Allodynia, Drug interaction, Intrathecal injection, N6-cyclohexyladenosine, Neostigmine
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