Korean J Anesthesiol.  2010 Jul;59(1):39-44. 10.4097/kjae.2010.59.1.39.

The interaction of intrathecal neostigmine and N(6)-cyclohexyladenosine on anti-allodynic effects in rats with a nerve ligation injury

• Choi DK
• Choi SS
• Hwang JH

• KMID: 2236486
• DOI: http://doi.org/10.4097/kjae.2010.59.1.39

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.

Keyword

Allodynia; Drug interaction; Intrathecal injection; N(6)-cyclohexyladenosine; Neostigmine

MeSH Terms

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
Adenosine
Cholinesterase Inhibitors
Neostigmine
Purinergic P1 Receptor Agonists