In the current study, we demonstrate that Tonabersat, an orally bioavailable Cx43 hemichannel blocker (NCT05727891), which has previously demonstrated a good safety profile in phase II clinical trials for migraine prophylaxis [104], reduces Cx43 hemichannel-mediated priming and activation of the NLRP3 inflammasome in RPTECs in response to high glucose and inflammatory cytokines. Here, GJA1 is linked to migraine disorder.