TAC1 and thalassemia: Low hemoglobin in thalassemia causes hypoxia and releases reactive oxygen species (ROS) through inhibition activity of oxygen-sensitive prolyl hydroxylases (PHDs), then causes the activation of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1).10,11 This protein activation will release substance P which plays the role in pain sensitization.12