Calcium channel blockers, which dilate arteries by reducing calcium flux into cells, effectively lower blood pressure, especially in combination with other drugs, and some formulations of agents of this class are approved for treating angina or cardiac dysrhythmias (Elliot, 2011).
Cav 3.2 T-type calcium channels are important regulators of pain signals in the afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore, it is reasonable to predict that inhibiting T-type calcium channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief (Snutch, 2018).
Existing evidence suggests that flunarizine, verapamil, nifedipine, and nimodipine are effective prophylactic agents in both common and classic migraine. Nifedipine and nimodipine also appear to be valuable for the treatment of cluster headache. Two case reports describing favorable responses to flunarizine in childhood hemiplegic migraine are the only available data concerning the utility of these drugs in "complicated" migraine syndromes. The role of Ca2+ channel antagonists in treating "muscle contraction" or "tension" headaches has not been addressed in any detail. (Greenberg, 1986)
Verapamil is a well-known calcium channel blocker and is the preferred medication to prevent cluster headaches. It is taken every day during a cluster cycle. Usually, the benefits of verapamil are more important than any minor side effects. The common side effects of this medicine include slowing of the heart rate, swelling in the lower legs or ankles, constipation or diarrhea, dizziness or lightheadedness, and flushing or feeling warm. Verapamil appears to be an effective prophylactic drug in the treatment of CH and despite the scarcity of controlled trials, it is still the drug of choice. (Peterson 2019)
Elliott WJ, Ram CV. Calcium channel blockers. J Clin Hypertens (Greenwich). 2011 Sep;13(9):687-9. doi: 10.1111/j.1751-7176.2011.00513.x. Epub 2011 Jul 27. PMID: 21896151.
Snutch TP, Zamponi GW. Recent advances in the development of T-type calcium channel blockers for pain intervention. Br J Pharmacol. 2018 Jun;175(12):2375-2383. doi: 10.1111/bph.13906. Epub 2017 Jul 12. PMID: 28608534; PMCID: PMC5980537.
Greenberg DA. Calcium channel antagonists and the treatment of migraine. Clin Neuropharmacol. 1986;9(4):311-28. doi: 10.1097/00002826-198608000-00001. PMID: 2425960.
Tso AR, Brudfors M, Danno D, Grangeon L, Cheema S, Matharu M, Nachev P. Machine phenotyping of cluster headache and its response to verapamil. Brain. 2021 Mar 3;144(2):655-664. doi: 10.1093/brain/awaa388. PMID: 33230532; PMCID: PMC7940170.
Petersen AS, Barloese MCJ, Snoer A, Soerensen AMS, Jensen RH. Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives. Headache. 2019 Sep;59(8):1198-1211. doi: 10.1111/head.13603. Epub 2019 Jul 24. PMID: 31339562.