The sham group is placed as a reference of the maximum possible effect.In all cases data are presented as mean SEM for animals, although SEM were <a href="http://www.targetmol.com/compound/Amitriptyline-hydrochloride">buy
Amitriptyline hydrochloride</a> omitted in the treatments with gabapentin, carbamazepine, benfotiamine and cyanocobalamin for the sake of clarity.Allodynia was observed in the rats hafter spinal nerve ligation and remained that way for at least days after the experiments were carried out. Oral administration of gabapentin, carbamazepine, benfotiamine and cyanocobalamin, but not vehicle, reduced tactile allodynia induced by ligation of LL spinal nerves and dosedependent, carbamazepine mgkg; higher doses of any drug did not produce greater antiallodynic effects.At the maximal doses tested, the combination of gabapentin or carbamazepine with either benfotiamine or cyanocobalamin completely recovered normal sensitivity in the neuropathic rats and dosedependent antiallodynic effect in the neuropathic rats. Of note, these dose combinations did not significantly modify motor coordination in the rotarod test. When data for combinations were submitted to isobolographic analysis, the experimental values of ED were lower than those expected from a purely additive interaction.The theoretically additive dose line depicts all points of the combinations yielding an effect of according to an additive interaction.For the four combinations, the experimental ED values clearly were situated below the theoretically additive dose line, indicating a synergistic interaction between these drugs. Effect of the high tested doses of gabapentin, carbamazepine, benfotiamine, cyanocobalamin and their combination on motor coordination in rats.Our results agree with the literature in showing that systemic gabapentin is able to reduce neuropathic pain in nerveinjured rats. This antiallodynic effect was accompanied by a significant reduction of motor coordination in the rotarod system with the highest dose tested.Our data agree with previous observations showing that gabapentin induces rotarod deficits or pronounced sedation at antinociceptive doses. Antiallodynic effects of gabapentin have been correlated with electrophysiological studies where the drug is able to reduce neuronal responses in spinal nerveligated rats. To date, sites and mechanisms responsible for the antiallodynic effect of gabapentin remain unclear.Other mechanisms, such as reduction in the release of excitatory amino acids through an indirect interaction with NMDA receptors, have been suggested. At the highest effective dose, carbamazepine produced nonsignificant rotarod deficits.The data agree with previous observations showing that systemic administration of carbamazepine is able to reduce neuropathic pain in several models of nerve injury in the rat. However, it is unlikely that the antiallodynic effect of carbamazepine could be due to its sedative effects, as the highest tested dose produced only a slight rotarod deficit.Moreover, the fact that systemic carbamazepine is also able to reduce spinal neuronal responses in spinal nerveligated rats is consistent with our data. The oblique line between thexaxis andyaxis is the theoretical additive line.At the highest tested doses, these drugs did not produce rotarod deficits in the rats.These results agree with previous observations from our group showing that cyanocobalamin and benfotiamine are able to reduce tactile allodynia in the spinal nerve ligation model in the rat. Therefore, results of this study confirm the efficacy of benfotiamine and cyanocobalamin in this type of pain.