title: The interaction of intrathecal neostigmine and N-cyclohexyladenosine on anti-allodynic effects in rats with a nerve ligation injury.
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 microg) and CHA (0.03-3 microg) 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dae Kee
authors.initials: DK
authors.lastname: Choi
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Choi
authors.forename: Jai Hyun
authors.initials: JH
authors.lastname: Hwang