Salivary Substance P, 5‐Hydroxytryptamine, and γ‐Aminobutyric Acid Levels in Migraine and Tension‐Type Headache

Abstract

Substance P, 5-hydroxytryptamine, and gamma-aminobutyric acid levels in saliva were measured in 55 patients with migraine during headache attacks (15 men and 40 women, average age 37.6 years), 36 patients with migraine in interictal periods (8 men and 28 women, average age 43.9 years), 48 patients with tension-type headache during headache attacks (18 men and 30 women, average age 47.3 years), and 25 patients with tension-type headache in interictal periods (10 men and 15 women, average age 48.6 years). Forty-three normal healthy volunteers composed the control group (17 men and 26 women, average age 32.7 years). Substance P levels in saliva were determined using competitive enzyme-linked immunosorbent assay, and were 26.9 +/- 45.1 pmol/mL in the patients with migraine during headache attacks, 30.0 +/- 59.7 pmol/mL in the patients with migraine in interictal periods, 243.5 +/- 1137 pmol/mL in the patients with tension-type headache during headache attacks, 101.3 +/- 364 pmol/mL in the patients with tension-type headache in interictal periods, and 21.2 +/- 17.4 pmol/mL in the healthy controls. 5-hydroxytryptamine levels in saliva were determined using reversed-phase high-performance liquid chromatography with electrochemical detection, and were 895 +/- 1075 ng/mL in the patients with migraine during headache attacks, 758 +/- 1375 ng/mL in the patients with migraine in interictal periods, 1646 +/- 1945 ng/mL in the patients with tension-type headache during active headache periods, 1167 +/- 1495 ng/mL in the patients with tension-type in headache-free periods, and 450 +/- 405 ng/mL in the healthy controls. Gamma-aminobutyric acid levels in saliva were determined using high-performance liquid chromatography with precolumn ortho-phthalaldehyde fluorescence detection. Gamma-aminobutyric acid levels in saliva were 36.8 +/- 49.8 pmol/mL in the patients with migraine during headache attacks, 17.9 +/- 25.2 pmol/mL in the patients with migraine in interictal periods, 16.0 +/- 18.3 pmol/mL in the patients with tension-type headache during active headache periods, 14.1 +/- 6.8 pmol/mL in the patients with tension-type headache in headache-free periods, and 21.6 +/- 22.7 pmol/mL in the healthy controls. The salivary substance P and 5-hydroxytryptamine levels in the patients with tension-type headache during active headache periods were significantly higher than those in healthy controls. In contrast, we found no significant differences between the salivary gamma-aminobutyric acid levels in the patients with tension-type headache and healthy controls. The high levels of salivary substance P and 5-hydroxytryptamine in tension-type headache patients during headache periods might reflect release of substance P from the pain sensory system. Saliva could represent a fluid particularly suitable to the study of neuropeptide release under specific conditions such as migraine and tension-type headache.