The interaction of intrathecal neostigmine and N-cyclohexyladenosine on anti-allodynic effects in rats with a nerve ligation injury

• Main Authors: Dae Kee Choi, Seong Soo Choi, Jai Hyun Hwang
• Format: Article
• Language: English
• Published: Korean Society of Anesthesiologists 2010-07-01
• Series: Korean Journal of Anesthesiology
• Subjects: allodynia; drug interaction; intrathecal injection; n-cyclohexyladenosine; neostigmine
• Online Access: http://ekja.org/upload/pdf/kjae-59-39.pdf

BackgroundNerve 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.MethodsMale 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.ResultsNeostigmine, 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.ConclusionsIntrathecal co-administration of neostigmine and CHA showed a synergistic anti-allodynia effect.