ESR1 and breast cancer: Estrogen can activate ClC-3 via ERα in the cell membrane of osteoblasts (Deng Z. et al., 2017), promote proliferation of ER+ breast cancer MCF-7 cells through the ClC-3 Cl– channel pathway (Yang et al., 2018), and regulate ion channels in pain modulation, but its effects on analgesia and promotion of pain are inconsistent (Berman et al., 2017; Ren et al., 2018).