A Murine Model of High Dietary Histamine Intake: Impact on Histamine Contents and Release in Neural and Extraneural...

Background: Histamine intolerance, a disorder due to impaired degradation of dietary histamine, is frequently associated with headaches, but the underlying pathophysiology is largely unknown; the sensitization of meningeal afferents appears likely. We approached this issue by examining histamine concentrations in different tissues and meningeal histamine release in a new mouse model of high-histamine diets. Methods: C57BL/6 mice of both sexes were fed with diets containing 3 or 9 g/kg histamine and compared to control groups. After 10-30 days, the histamine concentration was determined in plasma, samples of homogenized ileum, trigeminal ganglia, spinal medulla, and cerebellum using an ELISA. The histamine release from mast cells in the dura mater stimulated with compound 48/80 was also examined. Results: Animals supplied with high dietary histamine showed normal behavior and no signs of suffering. Compared with the controls, the histamine concentration was significantly higher in plasma and ileum of mice fed with 3 g/kg, highest in animals fed with 9 g/kg histamine. In addition, this group of animals showed also higher histamine concentrations in the trigeminal ganglion. The histamine release from the dura mater in mice supplied with 3 g/kg histamine was not significantly different to control animals, but the relative increase in stimulated release was lower in male animals of the high histamine group. Conclusions: High dietary histamine increases histamine levels in blood plasma and the gut, whereas the histamine content of neural tissues is not significantly influenced. The lowered stimulated release in animals subjected to high dietary histamine may indicate compensatory mechanisms.