Antinociceptive drug interaction between intrathecal vitamin E and gabapentin in the rat formalin test

Background: Gabapentin is thought to exert an effect through the voltagedependent calcium channel. Vitamin E is a widely known antioxidant which neutralizes the harmful effect of ROS which is considered to play a prominent role in various painful conditions. This study was therefore conducted to assess the antinociceptive effects of gabapentin and vitamin E and the interaction of these drugs in the modulation of pain in rats subjected to a formalin test. Methods: SpragueDawley rats with a lumbar intrathecal catheter were tested for their paw flinches by 5% formalin injection after intrathecal injection of gabapentin or vitamin E. After obtaining doseresponse curves for each drug, the effect of the combination was tested by the total dose fraction value and isobolographic analysis. Results: When a single drug was injected intrathecally, significant dosedependent decreases in flinches were shown only in the late phase. ED50 values of intrathecal gabapentin and vitamin E in the late phase were 75.3 ± 9.58ug, and 17.56 ± 1.65 mg/kg respectively. The combination of gabapentin and vitamin E produced dosedependent decreases in the number of flinches in both phases induced by the formalin test. The ED50 value of the combination was lower than the theoretical additive values in the late phase, but did not show a significant difference with the theoretical additive value. Conclusions: Gabapentin and vitamin E (by itself) have no antinociceptive effect in the early phase; however their combination has shown an antinociceptive effect. In addition, they show additive effects in the late phase of the formalin test.