I’ve had migraines since 2006, when I started college. The pain is excruciating, disabling, ruinous, usually on both sides of my head. I can sense a migraine coming 12-24 hours beforehand, in the form of a small sphere of ache embedded deep inside my brain that I can amplify if I shake my head once or twice vigorously. The onset is also accompanied by constipation and a growing throbbing pain, as if a part of my brain was swollen and pushing against blood vessels flowing on the inside of the skull. When the ache kicks in fully, I can feel my heart beat in my head.

There’s two ways the pain goes away – a heavy dose of paracetamol (500 mg) or by avoiding triggers. Only the latter is 100% effective, and it took me half a decade to figure out what some of the triggers were.

Although it’s recognised to be the most common form of disability worldwide, afflicting an est. one billion people, scientists don’t know what causes a migraine. It’s commonly believed that it’s a mix of environmental and genetic factors, with one twins study from 2007 suggesting the latter’s influence ranges from 34% to 51%. However, this hasn’t prevented researchers from developing medicines to fight it (in much the same way we don’t know how selective serotonin re-uptake inhibitors work but they’re widely prescribed to treat depression).

One study from 2006 noted that there are two prevailing theories about the genesis of migraines united by a common theme: “the generally accepted role of the trigeminal ganglion in the painful phase of migraine”. It is this commonality that a new class of drugs called CGRPR antagonists – including erenumab, galcanezumb and eptinezumab – appears to address. Their mechanism of action throws some light on our understanding of this debilitating syndrome.

The acronym stands for calcitonin gene-related peptide receptor. Calcitonin is a hormone secreted by cells in the thyroid gland; it is responsible for reducing calcium and phosphorous levels in the blood when they rise above a threshold. The peptide in question is involved in the transmission of nociception – an “intense chemical, mechanical or thermal stimulation of the sensory nerve cells”, carried by sensory cells called nociceptors to the brain.

According to one 2008 paper, a migraine could be the result of nociceptors in the brain stem (connected to the trigeminal ganglion by a single sensory root) becoming over-sensitised, with the CGRP involved in maintaining them in that state. Conversely, the CGRPR antagonists work against this state.

Erenumab was developed by Amgen and is being marketed under the name Aimovig. It was approved for use by adults by the FDA on May 17, 2018, following a phase III clinical trial involving 955 subjects over six months. It is to be administered as a subcutaneous injection once a month, of dose 70mg or 140 mg.

According to the trial paper, published in November 2017, “A 50% or greater reduction in the mean number of migraine days per month was achieved for 43.3% of patients in the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared with 26.6% in the placebo group.” But this is not entirely good news because one year’s worth of injections costs $6,900, which translates to Rs 39,000 per month.

Phase III trials for galcanezumab have been completed and Eli Lilly & Co., its maker, is awaiting FDA approval. Alder’s eptinezumab entered phase III trials in August 2017.