Opioids are a common treatment to relieve migraine pain. However, prolonged opioid use could increase migraine frequency and severity.

Researchers from University of Illinois at Chicago and colleagues suggest they have discovered a peptide linking migraine pain with pain induced by opioid overuse.

Their findings are published in the journal Molecular and Cellular Proteomics.

“Endorphin is an example of a peptide that signals the brain to give a ‘runner’s high.’ However, not all peptides signal for pleasant outcomes,” says Amynah Pradhan, senior author and UIC associate professor of psychiatry at the College of Medicine, in a media release from University of Illinois at Chicago.

“Pituitary adenylate cyclase-activating peptide, or PACAP, is a peptide that can induce migraines in migraine-prone individuals. Because the overuse of opioids can lead to worse migraines, we wanted to determine whether opioid-induced pain changed the amounts of peptides in the brain and understand if pain from migraines and opioid overuse shared any peptides in common.”

To study these peptides, Pradhan and her colleagues, including researchers at the University of Illinois at Urbana-Champaign, developed two mouse models: migraine pain and opioid overuse pain. Using mass spectrometry to identify peptides and their quantities in the animal samples, they found only a few peptides were altered in both models. PACAP was one of them.

“We were amazed to find PACAP in both models,” Pradhan shares. “This study validates prior work on PACAP’s role in migraine pain and, more importantly, is the first to identify PACAP as a factor in opioid-induced pain. It is also significant that the PACAP increase was seen in major pain-processing sites of the brain, in both models.

“These findings provide strong evidence that PACAP is involved in both migraine and opioid-overuse pain. We finally understand a mechanism through which opioids may exacerbate migraines — through PACAP.”

These findings may inform the development of real-world treatments, Pradhan suggests.

“Companies are developing therapies for migraine pain right now,” Pradhan adds. “There are clinical trials underway to test antibodies targeting PACAP and a PACAP-binding receptor. Based on our data, these therapies may be extremely effective for people that have used opioids to treat their migraines.”

This research may benefit people suffering from non-migraine pain as well, she concludes, as people with chronic pain also experience opioid-induced pain after overuse.

[Source(s): University of Illinois at Chicago, Science Daily]