The interaction of intrathecal neostigmine and N(6)-cyclohexyladenosine on anti-allodynic effects in rats with a nerve ligation injury.
10.4097/kjae.2010.59.1.39
- Author:
Dae Kee CHOI
1
;
Seong Soo CHOI
;
Jai Hyun HWANG
Author Information
1. Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. jhhwang@amc.seoul.kr
- Publication Type:Original Article
- Keywords:
Allodynia;
Drug interaction;
Intrathecal injection;
N(6)-cyclohexyladenosine;
Neostigmine
- MeSH:
Adenosine;
Animals;
Catheters;
Cholinesterase Inhibitors;
Drug Interactions;
Humans;
Hyperalgesia;
Injections, Spinal;
Ligation;
Male;
Neostigmine;
Neuralgia;
Purinergic P1 Receptor Agonists;
Rats;
Rats, Sprague-Dawley;
Spinal Nerves
- From:Korean Journal of Anesthesiology
2010;59(1):39-44
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 N(6)-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 microgram) and CHA (0.03-3 microgram) were administered to obtain the dose-response curves and the 50% effective dose (ED(50)). Equal fractions (1/2, 1/4 and 1/8 ED(50)s) of the two drugs were administered to establish the ED(50) 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 ED(50) 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.
