Clinical-Biochemical Correlates of Migraine Attacks in Rizatriptan Responders and Non-Responders

Abstract

The present study was aimed at verifying the clinical characteristics of a typical attack in 20 migraine patients, 10 responders and 10 non-responders to rizatriptan, and at investigating any differences in the levels of neuropeptides of the trigeminovascular or parasympathetic systems [calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP) measured by radioimmunoassay methods in external jugular blood] between responders and non-responders. In all responders to rizatriptan, pain was unilateral, severe, and pulsating, and in five of them at least one sign suggestive of parasympathetic system activation was recorded. Five patients who were non-responders to rizatriptan referred bilateral and non-pulsating pain, even though severe in most of them. CGRP and NKA levels measured before rizatriptan administration were significantly higher in responders than in non-responders (P < 0.0001 and P < 0.002, respectively). In the five patients with autonomic signs among rizatriptan responders, detectable VIP levels were found at baseline. One hour after rizatriptan administration, a decrease in CGRP and NKA levels was evident in the external jugular venous blood of rizatriptan responders, and this corresponded to a significant pain relief and alleviation of accompanying symptoms. VIP levels were also significantly reduced at the same time in the five patients with autonomic signs. After rizatriptan administration, CGRP and NKA levels in non-responder patients showed less significant variations at all time points after rizatriptan administration compared with rizatriptan responders. The present study, although carried out on a limited number of patients, supports recent clinical evidence of increased trigeminal activation associated with a better triptan response in migraine patients accompanied by parasympathetic activation in a subgroup of patients with autonomic signs. In contrast, the poor response seems to be correlated with a lesser degree of trigeminal activation, lower variations of trigeminal neuropeptides after triptan administration, and no evidence of parasympathetic activation at baseline.

Migraine and neuropeptides

“…VIP acts as a potential predictor of onabotulinumtoxin type A responders versus non-responders (Cernuda-Morollon et al, 2014). During spontaneous migraine attacks, the VIP level was significantly reduced in the external jugular venous blood after rizatriptan administration (Sarchielli et al, 2006b). In the saliva, the VIP level was significantly elevated interictally in migraine subjects as compared with controls, and following sumatriptan treatment the VIP level was significantly decreased during the migraine attack (Bellamy et al, 2006).…”

Negative predictors of clinical response to triptans in patients with migraine

“…Therefore, between consistent and inconsistent responders, the activation of the trigeminovascular system may be different. The poor response seems to be correlated with a lesser degree of trigeminal activation after rizatriptan administration [38]. Thus, in future study, we need to investigate the change of periorbital/deep orbital pain after the intake of triptans.…”

Triptan efficacy in migraine attacks: from appropriate diagnosis to metabolic profiles and pharmacogenomics

“…Another clinical distinguishing feature among migraine patients with better or poor response to triptan seems to be the lack or the presence of local autonomic signs during migraine headache, the latter being a positive predicting factor for better response to triptan [Barbanti et al, 2003]. Accordingly, increased trigeminal activation (as measured by CGRP and NKA levels in the external jugular vein blood) in patients with autonomic local signs relates with better response to rizatriptan [Sarchielli et al, 2006]. These issues need to be investigated further.…”