Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods

Abstract

Substance P (SP), calcitonin gene-related peptide (CGRP), and angiotensin converting enzyme (ACE) may have roles in trigeminovascular nociceptive mechanisms. We investigated interictal levels of SP, CGRP, ACE activity, and their correlation, in a sample of migraineurs. Forty-one patients suffering from migraine with aura (MA), 54 without aura (MO), and 52 non-headache subjects (controls) participated in this study. Blood samples were collected from cubital veins. Plasma levels of SP and CGRP were measured by enzyme immunoassay. Plasma ACE activities were measured spectrophotometrically. SP levels in MA (6.6+/-3.7 pg/ml; mean+/-SD) and MO (6.6+/-3.2 pg/ml) were significantly higher than in controls (4.8+/-2.4 pg/ml) (P<0.01). CGRP levels in MA (18.8+/-8.8 pg/ml) and MO (19.1+/-9.4 pg/ml) were also significantly higher than in controls (13.4+/-4.4 pg/ml) (P<0.01). ACE activities in MA (34.6+/-19.0 U/l) were significantly higher than in MO (25.3+/-13.2 U/l) and controls (27.0+/-20.4 U/l) (P<0.05). There was a significant correlation between SP and CGRP levels (P<0.05). In MA, SP and CGRP showed a tendency toward positive correlation, which was not significant. There was a weak, but significant positive correlation between SP levels and ACE activities (P<0.01). However, a relationship between ACE activities and CGRP levels was not observed. The data suggest that SP, CGRP, and ACE are relevant to migraine pathophysiology, and that they may interact.

Renin–angiotensin system in pain: Existing in a double life?

“…90 The preclinical studies showing an increase in pain perception (in terms of increase in the number of writhings) in the thermal and chemical nociception model of pain with captopril and losartan also suggests the pain-attenuating effects of endogenous AngII. 81 An active role of the endogenous RAS in producing analgesia is further supported by stress-induced analgesiabased studies. 84,86 Studies have shown a significant increase in renin-like activity in the hypothalamus and frontoparietal cortex in rats subjected to immobilization stress.…”

Current and prospective pharmacological targets in relation to antimigraine action

“…Furthermore, in migraine patients, (a) a strong correlation was found between plasma CGRP concentrations and migraine headache as the changes in plasma CGRP levels during migraine attacks significantly correlated with the headache intensity (Durham 2004;Iovino et al 2004;Petersen et al 2005b); (b) infusion of CGRP produced a migraine-like headache (Olesen et al 2004); and (c) baseline CGRP levels were increased in migraineurs (Fusayasu et al 2007). …”

“…In addition, genetic studies suggest an association between ACE gene polymorphisms and migraine (Paterna et al 2000). Further, ACE activity in migraine with aura is reported to be significantly higher than in migraine without aura and control subjects (Fusayasu et al 2007). Despite the above evidence, the role of angiotensin II in the pathophysiology of migraine should be clarified in animal models to understand the mechanism(s) of action involved.…”

Role of neuropeptides in migraine: where do they stand in the latest expert recommendations in migraine treatment?

“…Nevertheless, a increased plasma SP and CGRP levels and high angiotensin-converting enzyme (ACE) activity has been reported in migraineurs during headache-free periods [Fusayasu et al, 2007].…”