Background and Objective: Neuropathic pain remains a complex and poorly managed condition, with current treatments often associated with significant side effects. This study aims to evaluate and compare the effects of sumatriptan, baclofen and gabapentin on acute and chronic pain, focusing on their impact on neurotransmitters and neuropeptides. Materials and Methods: Acute and chronic pain models were evaluated in rats using the plantar analgesia meter, formalin test and sciatic nerve ligation (CCl) model. Drugs were administered intraperitoneally and pain responses were measured at 30, 60 and 90 min post-treatment. Biomarker analysis was conducted using ELISA to measure GABA, glutamate, substance P (SP) and Calcitonin Gene-Related Peptide (CGRP) levels in brain tissue. Statistical analysis was performed using GraphPad Prism® version 8, with significant differences determined by one-way ANOVA followed by Tukeyʼs post hoc  test for multiple comparisons (p<0.05). Results: In the acute pain model, no significant differences were observed between treatments. In the CCl model, gabapentin (GBP) produced the most significant reduction in pain, particularly at 30 and 60 min. The formalin test showed that GBP significantly reduced paw licking time during both acute and chronic phases compared to baclofen (BAC), sumatriptan (SUM) and control groups. Additionally, GBP and BAC increased GABA levels, while GBP and SUM reduced SP and CGRP levels. Glutamate levels remained unchanged across all groups. Conclusion: Gabapentin was the most effective in pain models, influencing key brain biomarkers, while baclofen and sumatriptan showed moderate effects.