Evaluation of PACAP Levels in Chronic Migraine

Levels of pituitary adenylate cyclase activating polypeptide (PACAP) found in the peripheral blood of women with chronic migraine did not reflect parasymphathetic activation in chronic migraine and were no different than levels seen in healthy women, according to the results of a study published in Headache.

PACAP levels were neither increased nor decreased in women with chronic migraine compared with a group of healthy women and a group of women with episodic migraine.

“Our results are surprising considering the proposed involvement of PACAP in migraine and in chronic migraine pathophysiology,” wrote researchers led by Eva Cernuda-Morollon, PhD, of University Hospital Central de Asturias, Oviedo, Spain. “In contrast to calcitonin gene-related peptide and vasoactive intestinal peptide, serum level of PACAP, as measured in cubital vein and by ELISA, does not seem to be a useful biomarker to test in this case the activity of the cranial parasympathetic arm of the trigemino-vascular system, at least interictally and in women with chronic migraine.”

According to the study, release of vasoactive intestinal peptide (VIP) is viewed as the explanation for the appearance of cranial parasympathetic symptoms in migraine headaches. Emerging evidence has also suggested that PACAP might also be involved in the appearance of these symptoms.

Therefore, in this study, the researchers evaluated whether blood levels of PACAP could serve as a biomarker for parasympathetic activation. They enrolled 86 women aged older than 17 with chronic migraine and assessed serum samples for PACAP and VIP levels obtained by the right antecubital vein. These results were compared with 32 healthy women and 35 women with episodic migraine.

There was no significant difference between PACAP levels in women with chronic migraine (109.8 pg/mL), healthy women (108.7 pg/mL), or women with episodic migraine (98.8 pg/mL). However, plasma samples did show that VIP levels were significantly increased among women with chronic migraine (136.0 pg/mL) compared with the healthy women (88.6 pg/mL; P=0.027). However, levels were not significantly different than those seen in women with episodic migraine (103.0 pg/mL).

“Even though our samples were processed immediately, our findings could also be due to the very short half-life of PACAP,” the researchers noted.

“In addition, it must be taken into account that any analysis of peptides in the peripheral circulation measures in fact peptides coming from the entire body. In line with this, a very recent study has found elevated ictal PACAP-38 levels in the external jugular vein in 15 migraine patients as measured by radioimmunoassay,” the researchers wrote. “Further research, therefore, is needed to clarify the actual implication of PACAP in migraine and in CM pathophysiology and its potential role as a migraine biomarker.”

Cernuda-Morollon E, Riesco N, Martinez-Camblor P, et al. No change in interictal PACAP levels in peripheral blood in women with chronic migraine. Headache. Epub 2016 Sep 16.