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Review
. 2021 Dec 9;7(4):298-308.
doi: 10.1002/ibra.12003. eCollection 2021 Winter.

Breakthroughs on the clinical management of headache and questions that need to be solved

Yu-Cong Liu  1 , Ting-Ting Yang  1 , Jing Li  1 , Hui-Chan Xu  1 , Shun-Lian Li  1 , Liu-Lin Xiong  2   3
Affiliations
Review

Breakthroughs on the clinical management of headache and questions that need to be solved

Yu-Cong Liu et al. Ibrain. .

Abstract

Headache is a common refractory disorder among adults, especially in females, which can lower the quality of life in patients and increase medical costs. Nearly 90% of people have been affected by headache disorders during their lifetime. The severe situation of headaches has drawn the attention of researchers in recent years. Although the mechanism of headache has not been fully understood by us, there are many effective preventive drugs and treatments available. This review is aimed to sum up the progress in clinical trials of headaches in the past 5 years.

Keywords: clinical trial; headache; mechanism; prevention; therapeutics.

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Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
Search results of headache disorders in the Pubmed. (A) Studies on migraine, cluster headache, tension‐type headache account for a large proportion in the headache field. (B) The studies on headaches are increased by years [Color figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
The common locations of different types of headaches. (A) Migraine is unilateral and usually appears in the temporal part of the head. (B) TTH is bilateral and usually appears in the frontal head. (C) CH is unilateral as well, which usually has been reported to locate at behind or near the eyes. CH, cluster headache; TTH, tension‐type headache [Color figure can be viewed at wileyonlinelibrary.com]
Figure 3
Figure 3
The location of CGRP receptors. Adapted from Edvinsson et al. CGRP receptors are located at the end of the trigeminovascular system and smooth muscle cells, no study reported to find CGRP receptors on the sensory axons. CGRP, calcitonin gene‐related peptide [Color figure can be viewed at wileyonlinelibrary.com]
Figure 4
Figure 4
The target of CGRP drugs, Triptans and Ditans. (A) The targets of erenumab and gepants are CGRP receptors on the vascular smooth muscle (VSM). (B) Mabs target CGPR itself. (C) Tripants stimulate the 5‐HT1B/1D(/1F) receptors on the VSM. (D) Ditans stimulate the 5‐HT1Freceptors on the VSM. 5‐HT, 5‐hydroxytryptamine; CGRP, calcitonin gene‐related peptide [Color figure can be viewed at wileyonlinelibrary.com]
Figure 5
Figure 5
Advances in recent studies on headache. The approval of the Lasmiditan cementing the position of 5‐HT drugs as the first‐line treatment of headache. Novel treatment like CGRP and BTA had been proved to be effective in treating headache. And plenty of nonpharmacological treatment also showed positive result in studies. For the mechanism of the headache, besides the trigeminovascular pathways, recent studies revealed that K‐ATP channel and five types of miRNAs may play crucial role in the pathogenesis of headache. Studies also demonstrated that hypoxia and the level of glutamate are the triggers of headache. 5‐HT, 5‐hydroxytryptamine; BTA, botulinum toxin serotypeA; CGRP, calcitonin gene‐related peptide [Color figure can be viewed at wileyonlinelibrary.com]
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