Levels of nitric oxide metabolites in cerebrospinal fluid in cluster headache.
The pathophysiology of cluster headache (CH) is only partly understood. Nitric oxide (NO), a potent vasodilator, has been suggested to be involved, and increased plasma levels of nitrite, a stable product on NO degradation, have been identified in the active period and in remission. The aim of our study was to investigate the role of NO in CH by measuring its oxidation products, nitrite and nitrate, in the cerebrospinal fluid (CSF), a biological compartment closer to the supposed focus of the disorder. We collected CSF from 14 episodic CH patients. Lumbar puncture (LP) was performed at two occasions: in active period between headache attacks, and in remission, not earlier than three weeks after the last CH attack. Eleven healthy volunteers served as controls. To estimate NO production, we determined the levels of NO-oxidation end products (NOx), that is, the sum of nitrite and nitrate, by using capillary electrophoresis. CH patients in the active period had significantly increased NOx levels (mean 9.3, 95% confidence interval [CI] 8.5-10.1) compared with those in remission (mean 7.6, 95% CI 6.9-8.2; p < 001) and control subjects (mean 6.2, 95% CI 4.9-7.5; p < 0.001). CH patients also had statistically significant enhanced NOx levels in remission compared with those of control subjects (p = 0.034). CSF was also analysed with regard to inflammatory parameters and protein content. CSF showed signs of pleocytosis or oligoclonal bands or albumin increase in 43% of CH patients although these results were not conclusive. We suggest that CH patients have a generally raised NO tonus, both in the active period and in remission. We interpret these results as indications of a basal hyperfunction of the L-arginine-NO pathway, possibly as an expression of inflammatory activity, and sensitization of pain pathways. This is the first study analysing NOx in CSF in CH, and the results support NO involvement in the pathogenesis of CH.
Karolinska Institute, Sweden. anna.steinberg@karolinska.se
Anna
A
Steinberg
N Peter
NP
Wiklund
Lou
L
Brundin
A Ingela M Nilsson
AI
Remahl
D000328:Adult; D003027:Cluster Headache / Q000134:cerebrospinal fluid*; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000134:cerebrospinal fluid*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000134:cerebrospinal fluid*
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide