The study investigates the role of TRPA1 in mediating formalin-induced pain. Formalin, a widely used model for evaluating analgesic compounds, induces a biphasic pain response in laboratory animals. The first phase is thought to result from direct activation of primary afferent sensory neurons, while the second phase reflects central sensitization. The research shows that formalin activates sensory neurons by directly activating TRPA1, a cation channel involved in inflammatory pain. Formalin caused robust calcium influx in cells expressing cloned or native TRPA1 channels, and these responses were attenuated by a TRPA1-selective antagonist. Sensory neurons from TRPA1-deficient mice lacked formalin sensitivity. Pharmacologic blockade or genetic ablation of TRPA1 significantly reduced the characteristic flinching, licking, and lifting responses to formalin. These findings demonstrate that TRPA1 is the primary site of formalin's pain-producing action and that activation of this channel underlies the physiological and behavioral responses associated with formalin-induced pain hypersensitivity.The study investigates the role of TRPA1 in mediating formalin-induced pain. Formalin, a widely used model for evaluating analgesic compounds, induces a biphasic pain response in laboratory animals. The first phase is thought to result from direct activation of primary afferent sensory neurons, while the second phase reflects central sensitization. The research shows that formalin activates sensory neurons by directly activating TRPA1, a cation channel involved in inflammatory pain. Formalin caused robust calcium influx in cells expressing cloned or native TRPA1 channels, and these responses were attenuated by a TRPA1-selective antagonist. Sensory neurons from TRPA1-deficient mice lacked formalin sensitivity. Pharmacologic blockade or genetic ablation of TRPA1 significantly reduced the characteristic flinching, licking, and lifting responses to formalin. These findings demonstrate that TRPA1 is the primary site of formalin's pain-producing action and that activation of this channel underlies the physiological and behavioral responses associated with formalin-induced pain hypersensitivity.