Botulinum toxin type a therapy in migraine: preclinical and clinical trials.

Background: Botulinum toxin type A (BTX-A) has been reported to be effective for the therapy for migraine. The purpose of this study was to investigate the effect of BTX-A on the immunoreactive levels of calcitonin gene-related peptide (CGRP) and substance P (SP) in the jugular plasma and medulla oblongata of migraine in rats induced by nitroglycerin (NTG), and then to evaluate and compare the effectiveness of fixed (muscle)-sites and acupoint-sites injection of BTX-A for migraine therapy of patients in a randomly controlled trial extending over four months.

Materials And Methods: Rats with NTG-induced migraine were subcutaneously injected with vehicle or BTX-A (5 U/kg or 10 U/kg bodyweight). CGRP- and SP-like immunoreactivity (CGRP-LI and SP-LI) were determined by radioimmunoassay. In clinical trials, sixty patients respectively received BTX-A (2.5 U each site, 25 U per patient) at fixed-sites (group F, n = 30) including occipitofrontalis, corrugator supercili, temporalis and trapezius or at acupoint-sites (group A, n = 30) including EX-HN3, EX-HN5, GV20, GB8, GB20 and BL10.

Results: Local BTX-A injection suppressed NTG-induced CGRP-LI and SP-LI levels in jugular plasma and oblongata. BTX-A injection for both groups with migraine significantly reduced the attack frequency, intensity, duration and associated symptoms. The efficacy of BTX-A for migraine in group A (93% improvement) was more significant than that in group F (83% improvement) (P < 0.01).

Conclusions: The evidence that BTX-A decreases NTG-induced CGRP-LI and SP-LI levels in trigeminovascular system suggests that BTX-A attenuates migraine by suppression of neuropeptide release. BTX-A injections for migraine at acupoint-sites and fixed-sites are effective. Acupoint-sites BTX-A administration shows more efficacy for migraine than fixed-sites application.