Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood loss during surgery. However, a serious adverse effect of TXA is seizure due to inhibition of γ–aminobutyric acid (GABA) and glycine receptors in cortical neurons. These receptors are also present in the spinal cord, and antagonism of these receptors in spinal dorsal horn neurons produces painrelated phenomena, such as allodynia and hyperalgesia. Moreover, some patients who are injected intrathecally with TXA develop severe back pain. However, no previous studies have investigated whether TXA modulates the GABA and glycine receptors in dorsal horn neurons. We hypothesized that TXA inhibits both GABA and glycine receptors in dorsal horn neurons,resulting in producing pain. Here, we investigated the effects of TXA by using behavioral measures in rats and found that TXA produces behaviors indicative of spontaneous pain and allodynia. We then performed wholecell patch–clamp experiments that showed that TXA inhibits GABA_A and glycine receptors in spinal dorsal horn neurons. Finally, we also showed that TXA facilitates activation of the extracellular signal–regulated kinase in the spinal cord. These results indicated that TXA produces pain by inhibiting GABA_A and glycine receptors directly located on postsynaptic sites of the recorded SG neurons. In addition, TXA enhances the excitability of excitatory interneurons via blockade of GABAergic and glycinergic postsynaptic inhibition, which facilitates excitatory transmission to the SG neurons indirectly.