Abstract
Dear Sir We are pleased that Mavromichalis shared our conclusions on the casual association between the Helicobacter pylori infection and migraine. He proposed, as a possible explanation of the negative result, the lack of any pathogenic role of the infection in the inflammation of the gastric and duodenal mucosa. This suggestion is based on a non-controlled clinical series of 31 patients. Had Mavromichalis performed a case-control study with a larger number of cases, his conclusions would have been better supported (1).
We are aware that several authors reported a higher prevalence of H. pylori infection in migraineurs (2). However, in our study none of the controls and only 16.7% of patients with migraine were serologically positive for H. pylori infection. This difference was not statistically significant (P = 0.06), in agreement with other studies. Besides, our results showed that plasma accumulation of lipid peroxidation by-products, an index of the oxidative status, was increased in migraineurs with respect to healthy controls, while no difference was found between migraineurs with and without H. pylori infection (3). Although H. pylori may generate superoxide radicals, the absence of any difference in lipid peroxidation by-products between migraineurs with or without H. pylori infection suggests that in migraineurs serologically positive to H. pylori the bacterial release of oxidative by-products is localized into the gastric mucosa and inadequate to produce any systemic effect (3). Several other factors, including vascular tone, cerebral blood flow and metabolism disorders, smoking habit, diet, or extra-intestinal infections, might increase the oxidative status in migraineurs (4–6). The reported observation that H. pylori eradication significantly decreased migraine attacks (2) does not necessarily imply a causal role of this infection in migraine, because antibiotic treatments have widespread and multiple target effects. However, the reason for the increased vulnerability to oxidative stress that was found in migraineurs might be clarified investigating cerebral blood flow changes, the shear stress phenomenon, and the endogenous protective antioxidant mechanisms (7).
Mavromichalis also suggested that upper gastrointestinal mucosal inflammation might play an important role in the pathogenesis of migraine (1). This further hypothesis was based on his observation of a remarkable effect of anti-ulcer drugs in preventing migraine attacks. Unfortunately, the study by Mavromichalis was an incomplete single-blind, non-randomized trial with partial cross-over. Moreover, the author acknowledged that the proposed mechanism by which gastrointestinal mucosal inflammation might produce migraine required further verification. A well-conducted, multicentre, double-blind, randomized large clinical trial is mandatory in this field. We recognize that the role of gastrointestinal mucosal inflammation in the pathogenesis of migraine needs proper consideration. The effects on the mucosal nerve endings of bradykinin, histamine, serotonin, substance P, leukotrienes or prostaglandins, generated or released in the presence of inflammation, is the proposed mechanism by which inflammation produces pain and changes in the cerebral blood flow in migraine (1). How those changes might increase oxidative status remains to be clarified.