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

Choi DK, Choi SS, Hwang JH - Korean J Anesthesiol (2010)

Bottom Line: 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.Intrathecal co-administration of neostigmine and CHA showed a synergistic anti-allodynia effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Dose-response curves from the peak effects of percent maximal possible effect (%MPE) for anti-allodynia in the neostigmine, N6-cyclohexyladenosine, and their combination subgroups. These curves show a dose-dependent anti-allodynic effect. Data are expressed as mean ± SEM. Doses (µg) are represented logarithmically on the x axis and peak %MPE of each group is represented on the y axis. CHA: N6-cyclohexyladenosine, Neo: neostigmine, Neo-CHA: combination of neostigmine and N6-cyclohexyladenosine. *P < 0.05 compared with baseline value in each group.
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Figure 1: Dose-response curves from the peak effects of percent maximal possible effect (%MPE) for anti-allodynia in the neostigmine, N6-cyclohexyladenosine, and their combination subgroups. These curves show a dose-dependent anti-allodynic effect. Data are expressed as mean ± SEM. Doses (µg) are represented logarithmically on the x axis and peak %MPE of each group is represented on the y axis. CHA: N6-cyclohexyladenosine, Neo: neostigmine, Neo-CHA: combination of neostigmine and N6-cyclohexyladenosine. *P < 0.05 compared with baseline value in each group.

Mentions: IT administration of neostigmine, CHA, and their combination produced a dose-dependent anti-allodynic effect (Fig. 1). The maximal anti-allodynia effects occurred within 30 min, and then decreased gradually to baseline with the passage of time. The patterns of time-effect course were similar in all groups (data not shown).


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

Choi DK, Choi SS, Hwang JH - Korean J Anesthesiol (2010)

Dose-response curves from the peak effects of percent maximal possible effect (%MPE) for anti-allodynia in the neostigmine, N6-cyclohexyladenosine, and their combination subgroups. These curves show a dose-dependent anti-allodynic effect. Data are expressed as mean ± SEM. Doses (µg) are represented logarithmically on the x axis and peak %MPE of each group is represented on the y axis. CHA: N6-cyclohexyladenosine, Neo: neostigmine, Neo-CHA: combination of neostigmine and N6-cyclohexyladenosine. *P < 0.05 compared with baseline value in each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2908226&req=5

Figure 1: Dose-response curves from the peak effects of percent maximal possible effect (%MPE) for anti-allodynia in the neostigmine, N6-cyclohexyladenosine, and their combination subgroups. These curves show a dose-dependent anti-allodynic effect. Data are expressed as mean ± SEM. Doses (µg) are represented logarithmically on the x axis and peak %MPE of each group is represented on the y axis. CHA: N6-cyclohexyladenosine, Neo: neostigmine, Neo-CHA: combination of neostigmine and N6-cyclohexyladenosine. *P < 0.05 compared with baseline value in each group.
Mentions: IT administration of neostigmine, CHA, and their combination produced a dose-dependent anti-allodynic effect (Fig. 1). The maximal anti-allodynia effects occurred within 30 min, and then decreased gradually to baseline with the passage of time. The patterns of time-effect course were similar in all groups (data not shown).

Bottom Line: 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.Intrathecal co-administration of neostigmine and CHA showed a synergistic anti-allodynia effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus