Association of parthenolide and salicin as a preventive treatment on a migraine model induced by dural inflammatory soup application

ABSTRACT: Parthenolide (PTL) and salicin (SA), the main active components in Feverfew (Tanacetum parthenium) and White Willow (Salix alba), respectively, have been traditionally used as a remedy for various types of pain, including headaches. Because PTL and SA have different mechanisms of action, we hypothesize that a combination of these drugs would result in an additive effect. We investigated the effects of local and/or systemic administration of PTL, SA, or their combination on cephalic mechanical hypersensitivity (MH) in acute and chronic model of migraine induced by dural application of inflammatory soup (IS) in rats of both sexes. We also studied the effect of combination of PTL and SA on the sensitization of the trigeminocervical complex (TCC) induced by IS application using immunohistochemical (calcitonin gene-related peptide [CGRP] expression) and electrophysiological approaches. When combining low doses of PTL (2.5 mg/kg) and SA (5 mg/kg), we found that single systemic administration of combination prevented acute cephalic MH only in females. However, when administered daily, the combination prevented both chronic ictal and interictal cephalic MH as well as the IS-induced increase in CGRP-immunoreactivity within the TCC, in both sexes. Notably, a single dural application of the combination also prevented acute sensitization of TCC wide dynamic range neurons. Combining PTL and SA have an antimigraine effect in both male and female rats. The combination exerts its preventive effect, at least in part, by blocking the afferent inputs from the dura during the induction phase, preventing thus the establishment of central sensitization.