Effect of Ivabradine on Levcromakalim-Induced Symptoms in Individuals With Migraine Without Aura (ILIM)

Hyperpolarization-activated cation (HCN) channels have recently been implicated in neuropathic and inflammatory pain processes through their hyperfunction and/or overexpression. HCN channels may play a significant role in migraine pathophysiology, as 1) both an inflammatory and a neuropathic component has been hypothesized to contribute to migraine, and 2) HCN channel activity is facilitated by cyclic nucleotides, e.g. cAMP and cGMP (molecules thought to be central in migraine pathophysiology) and increases in extracellular K+ concentration. Opening of adenosine 5'-triphosphate-sensitive potassium channels (KATP channels) using Levcromakalim causes migraine attacks with and without aura in a high proportion of patients. KATP channel activation leads to hyperpolarization, which in turn could increase the open probability of HCN channels. This study aims to explore the effects of Ivabradine on Levcromakalim-induced migraine in individuals with migraine without aura. The investigators anticipate that this project will contribute greatly to the current understanding of migraine pathophysiology and the hypothesized role of HCN channels in migraine pain mechanisms. This is of great interest in future research, as such knowledge is an important prerequisite for further investigation and understanding of intracellular signalling mechanisms in migraine, which in turn will lead to the development of more effective and mechanism-based drugs.