Nitric oxide pathway and response to nitroglycerin in cluster headache patients: plasma nitrite and citrulline levels

Nitric oxide (NO) may participate in the mechanisms underlying vascular headaches,
such as migraine and cluster headache (CH), by triggering neurogenic
inflammation and activation of fibres conveying nociceptive inputs to the trigeminal
ganglion. Similarly to migraine, the administration of the NO donor glyceryltrinitrate
(GTN) to CH patients is a known model of inducing spontaneous-like
attacks. We carried out a GTN test (0.9 mg, sublingually) in 18 patients with
episodic CH in active phase and 12 controls. The plasma levels of NO metabolite
nitrites (NO
2
–
), after conversion of nitrates to NO
2
–
, were measured spectrophotometrically
at baseline, at the maximum intensity of the induced response (or
45 min after GTN in controls), and 120 min after GTN administration. The basal
plasma levels of L-citrulline were also assayed in patients and controls using highperformance
liquid chromatography. Basal NO
2
–
levels, similar in GTN-responsive
patients and controls (48.3
±
10.6 and 44.6
±
9.5
m
mol/l, respectively) were found
to be increased significantly at pain peak in patients (76.1
±
10.2
m
mol/l) and after
45 min in controls (78.2
±
9.6
m
mol/l) (
P
<
0.01 vs. respective baseline values), but
not after 120 min, without differences between groups. L-citrulline levels in basal
conditions showed no differences between groups (patients 64.8
±
11.7, controls
67.3
±
10.8
m
mol/l). These data do not support the presence of a basal hyperactivity
of the L-arginine–NO pathway in CH patients. Increased NO production may
be of importance in the mechanisms leading to CH attacks, but other factors
are likely to render CH patients hyperresponsive to NO, and ultimately to cause
the occurrence of pain and associated features