Introduction: The transmission and perception of pain are complex processes involving both the central and peripheral nervous systems. In general, pain impulses are generated, propagated, and sustained by the liberation of various autocoids, ions, and neurotransmitters at various points between the site of tissue damage, along the afferent sensory fibers, and within the spinal cord and brain. One of the most important inhibitors of pain is the GABAergic system. Isoniazid is a drug of choice as a first-line defense against active and latent tuberculosis. It is also involved in pain modulation in high doses by decreases the GABA levels of the brain. However, some studies showed that low-dose isoniazid has GABA-elevating effects. Methods: In order to study the antinociceptive effects of IP injection of Isoniazid male Wistar rats (200-270 g) was performed. Isoniazid (25, 50, 75 mg/kg, IP) was administered 60 minutes prior to formalin injection (50 μl of 4%). Then, formalin-induced paw jerking, and licking behaviors were recorded for 1 h. Results: The results of current study showed that Isoniazid (25, 50 mg/kg, IP) did not have any significant effects on flexing duration in the first phase but could significantly reduce it in the second phase of the formalin test (P<0.05, and P<0.001, respectively). While 75 mg/kg of Isoniazid (IP) significantly reduced flexing duration in the both first (P <0.05) and second (P<0.001) phases of formalin-induced pain. Conclusion: Consequently, the revealing results showed that 75 mg/kg of Isoniazid has an antinociceptive effect on behaviors in both the first and second phases of the formalin test, and it could consider as the effective dose for future formalin-induced pain studies.
