Background and Aim: Isoniazid is an antibiotic of choice for the treatment of different forms of tuberculosis. This drug by penetration into the brain may modulate the GABAergic system of the brain. Modulation of the GABAergic system of the brain may have analgesic effects. Therefore, the present research aimed to evaluate the possible analgesic effects of isoniazid in the formalin test. Methods: Thirty male Wistar rats (200-270 g) were divided into 5 groups (n=6). Three experimental groups received isoniazid (25, 50, 75 mg/kg, IP). The two other groups, as controls, received saline or nothing. Saline or isoniazid was administered 60 minutes before formalin injection (50 μl of 4%). Then, formalin-induced paw jerking, and licking behaviors were recorded for 1 h. Results: The results showed that isoniazid (25, 50, 75 mg/kg, IP) significantly reduced paw jerking frequency both in the first and second phases of the formalin test in the experimental groups compared to the saline-treated group (P<0.001). Moreover, isoniazid (25, 50, 75 mg/kg, IP) decreased the licking duration both in the first phase (P< 0.05, P< 0.05, and P< 0.01, respectively) and the second phase (P< 0.001) of the formalin test, significantly. Conclusion: Consequently, the results showed that isoniazid had analgesic effects in both phases of the formalin test and its highest effect was at the dose of 75 mg/kg.
