Pathophysiology of migraine chronification

In approximately 3% of migraineurs, migraine evolves into more protracted and severe conditions annually. Meanwhile, approximately 26% of chronic migraine cases regain the episodic nature of migraine headaches in two years. The prevalence of chronic migraine is estimated to be approximately 1%. Although the pathophysiology of migraine chronification is poorly understood, several studies have demonstrated abnormalities in pain processing mechanisms. Of note, the descending pain inhibitory system has been found to be defective in chronic migraine patients. Topiramate appears to ameliorate the disease conditions by correcting such abnormalities in the pain processing mechanisms. Neurogenic inflammation around the dural trigeminal afferents is known to play an important role in the generation of migraine attacks. Botulinum neurotoxins inhibit regulated exocytosis at the nerve terminals by cleaving the SNARE protein, SNAP25. As a result, release of migraine-related neuropeptides, calcitonin gene-related peptide and substance P, is reduced. Moreover, the insertion of transient receptor potential vanilloid subfamily, member 1 (TRPV1) into the plasma membrane is hindered by BoNT-A. We have demonstrated that the inability of TRPV1 to translocate to the plasma membrane results in its proteasome-mediated degradation within the trigeminal ganglion neurons, which may be relevant to the efficacy of BoNT-A against chronic migraine.