CGRP & Migraine Treatment

Part 7: CGRP—The Neuropeptide that Revolutionized Migraine Treatment

Every once in a while, the discovery of a single biological pathway changes how we understand an entire disease.

For migraine, one of those discoveries was CGRP—calcitonin gene-related peptide.

If you're an acupuncturist, you may wonder why understanding a pharmaceutical target matters when prescribing medication isn't within your scope of practice.

The answer is simple: CGRP medications have taught us an enormous amount about migraine physiology.

And in 2024, that science became strong enough to fundamentally change migraine treatment recommendations.

What Is CGRP?

CGRP is a neuropeptide—a small signaling molecule released by neurons.

It is found throughout the nervous system, but for migraine, we're particularly interested in CGRP released from sensory neurons associated with the trigeminovascular system we discussed in Part 6.

When this system becomes activated, CGRP can be released from trigeminal sensory fibers. Among its many actions, CGRP is a remarkably potent vasodilator and participates in nociceptive and inflammatory signaling.

But here's where the story becomes much more interesting.

Researchers found that CGRP levels can rise during migraine attacks, that successful treatment can normalize those elevations, and—perhaps most compellingly—that administering CGRP experimentally can actually provoke migraine attacks in susceptible individuals.

That made CGRP much more than an interesting biomarker.

It became a therapeutic target.

A New Generation of Migraine Medications

Historically, most medications used to prevent migraine weren't actually developed for migraine.

Patients were prescribed drugs originally developed for other conditions, including:

antiseizure medications
beta blockers
antidepressants
antihypertensive medications

Some of these medications can be very effective. But their effectiveness in migraine was discovered somewhat indirectly.

CGRP-targeting medications represented something different: migraine-specific therapies developed from our growing understanding of migraine biology.

These include monoclonal antibodies targeting CGRP or its receptor, as well as small-molecule CGRP receptor antagonists known as gepants.

And their effectiveness helped validate something researchers had suspected for decades:

CGRP isn't merely present during migraine. It is an important participant in migraine pathophysiology.

In 2024, Something Important Changed

For years, many patients couldn't access CGRP-targeting preventive medications until they had first tried—and failed—older, typically less expensive preventive medications.

This system of step therapy meant that insurance coverage often influenced the order in which patients received treatment.

Then, in 2024, the American Headache Society issued an important position statement.

After reviewing the accumulating evidence for efficacy, safety, and tolerability, the AHS concluded that CGRP-targeting therapies should be considered a first-line option for migraine prevention and that patients should not be required to fail other preventive medications first.

That was a significant change.

It acknowledged that migraine-specific treatments didn't necessarily belong at the end of the treatment algorithm simply because they were newer or more expensive.

Acupuncture and CGRP: An Interesting Paradox

Acupuncture needles don't interact with an empty landscape.

Skin and connective tissues are richly innervated by sensory fibers, including fibers containing neuropeptides such as CGRP. Mechanical stimulation of peripheral sensory nerves can participate in local neurovascular and neuroimmune responses.

This creates an interesting paradox.

In some contexts, sensory stimulation and CGRP-mediated responses may participate in beneficial local physiologic effects. But within a sensitized trigeminovascular system, CGRP is also intimately involved in migraine.

Clinically, this raises an intriguing question.

Occasionally, a highly sensitive migraine patient will tell you:

"If you put acupuncture needles in my scalp, it can trigger a migraine."

That experience should not be dismissed.

We cannot currently say that scalp acupuncture triggers migraine because it releases CGRP—the evidence isn't strong enough to establish that causal pathway. But it is biologically plausible that stimulating an already sensitized trigeminal sensory network could increase afferent and neuropeptide signaling enough to contribute to an attack in a susceptible patient.

For the clinician, the practical lesson is simpler:

Listen to the nervous system in front of you.

If a patient tells you scalp needling reliably triggers their migraine, you don't need to prove the mechanism before honoring that information.

The Bigger Lesson From CGRP

Perhaps the most interesting thing about CGRP isn't the medication at all.

It's what CGRP taught us about migraine.

Migraine isn't simply abnormal blood vessels.

It isn't simply inflammation.

And it isn't simply pain.

It involves a complex conversation between sensory nerves, neuropeptides, blood vessels, immune signaling, and central nervous system networks.

CGRP gave researchers one doorway into that conversation—and changed migraine treatment in the process.

Continue Rethinking Migraine

This is Part 7 of the Rethinking Migraine series.

Previous Article → Part 6: Why Pain Doesn't Begin Where You Think It Does

Next Article → Part 8: Why Light Hurts During a Migraine

Get CEUs on the topic! Migraines: A Clinical Guide for Acupuncturists, a comprehensive continuing education course designed to bridge modern neuroscience with acupuncture practice is available through Net of Knowledge.

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