Acute migraine attacks cause great pain to the patient and are disabling. Once the painkillers - even the triptans are ineffective or the patient has contraindications, the above problems will worsen. In recent decades, headache experts have been working on the development of new migraine treatments, which believe that relatively desirable treatments should avoid vasoconstriction.

Calcitonin gene-related peptide receptor antagonist

In the past 30 years, calcitonin gene-related peptide (CGRP) has been considered to play an important role in the pathophysiological process of some primary headaches. Over the past 3-5 years, targeting CGRP signaling-related drugs has been seen as one of the most promising treatments for migraine.

A related study in 2013 found that CGRP receptor antagonists can effectively prevent migraine, but due to its hepatotoxic side effects, it may not be safe to consider clinical application. Two randomized, controlled, double-blind, phase II trials conducted in 2014 suggested that the two CGRP antibodies, ALD403 and LY2951742, significantly reduced the number of days of migraine attacks per month compared with the placebo group.

In the ALD403 trial, 174 migraine patients were randomized to either the ALD403 group or the placebo group; the results showed that the ald403 migraine group had an average reduction of 5.6 days in migraine days within 28 days, compared with a corresponding reduction in the placebo group. It took 4.6 days.

In the LY2951742 trial, 217 patients were randomized to receive LY2951742 or placebo alone; the results showed that after 12 weeks, LY2951742 reduced the number of days of migraine attacks by 4.2 days in 28 days, compared with 3.0 days in the control group.

None of the patients in the two studies had safety concerns or serious drug side effects associated with CGRP antibodies; in addition, approximately 16% of patients had complete relief of headache after receiving medication; and for most patients, these effects persisted For a few months.

These results were significant because the patients included in the two studies were resistant to most drugs. In any case, the above new la antibody represent a promising way to prevent migraine, and it appears that the side effects of the drug are mild and the patient is well tolerated.

Pituitary adenylate cyclase activating receptor

Last year, another crucial study was the development of the pituitary adenylate cyclase-activated peptide-38 (PACAP) pathway. PACAP has been shown to have the ability to induce migraine-like episodes in migraine patients; this is not the case with vasoactive intestinal peptide (VIP) associated with its structure. A study from Copenhagen compared the ability of PACAP and VIP to induce migraine-like episodes in migraine patients, and the results showed that PACAP was more inducible.

The pituitary adenylate cyclase activating receptor (PAC1) has a much higher affinity for PACAP38 than VIP. Therefore, the PAC1 receptor may play an important role in migraine attacks, and it may be a promising target for future migraine treatment research.

Botulinum neurotoxin type A

In 2014, preclinical trials of the mechanism of action of botulinum neurotoxin type A (BoNT-A) in the treatment of chronic migraine brought enlightenment to subsequent studies.

It is unclear why BoNT-A is effective in treating chronic migraine, but it does not help with paroxysmal or stressful pain. Dr. Burstein and colleagues have recently discovered that BoNT-A can selectively inhibit meningeal nociceptors and prevent or reverse C-fiber-mediated mechanical hyperalgesia.

Clinically, migraine usually worsens after physical activity, such as bending or sneezing. The study suggests that BoNT-A prevents migraine by reducing the sensory signals generated by peripheral mechanical-nociceptors. As to whether the intracranial and extracranial structures are affected, further research is needed.