DB-03 - OnabotulinumtoxinA reduces percentage of activated dural pro-inflammatory macrophages and increases percentage of dural anti-inflammatory macrophages in response to CSD in female mice.

Cortical spreading depression (CSD), has been shown to cause inflammation and activation of nociceptive axons and macrophages (MPs) in the dura. We found that LPS increases a contracting MP behavior, whereas IL-10 causes MPs to expand, suggesting that they are M1- and M2-polarized MPs, respectively. OnabotA impacts dural MPs in female mice in 3 ways: (a) it reduces their overall number within the dura, (b) it reduces percentage of pro-inflammatory M1 MPs, and (c) it increases percentage of anti-inflammatory M2 MPs. Collectively, these results define a potentially novel understanding of the mechanism of action for onabotA in migraine prevention. Additionally, the inability of CSD to significantly activate dural MPs in males may provide insights into the phenotypic differences between males and females in migraine pathophysiology.