The role of calcitonin gene-related peptide in migraine prevention by botulinum toxin type A 1

Objectives: Calcitonin gene-related peptide (CGRP) is currently considered to be a major contributing factor in migraine headache. Botulinum toxin type A (BTXA) was found to be effective in migraine prevention. However, the mechanism of action in patients was unknown. Using injection as in clinical setting, the study aimed to determine whether BTXA could decrease the sensitization of the trigeminovascular nociceptive system through the reduction of CGRP action. Methods: Adult male Wistar rats were pretreated with normal saline solution or BTXA before KCl application to induce cortical spreading depression (CSD) or NaCl application as a control. Regional cerebral blood flow at parietal cortex was measured for 90 min after KCl or NaCl application. Tissues from trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) were then collected for CGRP and c-Fos measurement respectively. Results: BTXA pretreatment significantly decreased the cumulative blood flow and number of hyperemic peaks induced by KCl. Numbers of CGRP positive cells at TG and c-Fos positive cells at TNC were also reduced by BTXA. Conclusion: BTXA pretreatment reduced CGRP production and release from the TG leading to lessen CSD production and persistent activation of TNC which played a major role in migraine headache.