PROJECT SUMMARY:
Empirical evidence suggests that application of osteopathic manipulative treatment (OMT) to migraine
patients may reduce the frequency and pain intensity of headache episodes and provide abortive relief during
the migraine episode. The benefit of OMT has not been rigorously tested, however. The goal of this proposal is
to determine the possible efficacy and mechanisms of action of OMT as a preventative or acute therapy for
migraine. Our project is innovative because we use a preclinical model that recapitulate aspects of migraine
pathology including well-accepted “biomarkers” and clinical-relevant output measures that increase confidence
in translation across species. These studies will provide solid evidence to determine the possible utility of OMT
for clinical management of migraine. Migraine attacks commonly associate with nausea, vomiting and
hypersensitivity to a variety of external stimuli including light touch. The sufferers are mostly forced to reduce
their daily routine activities and lay down in a quiet, dark room to wait for the symptoms pass. The
pathophysiology of migraine is not well understood but ultimately, migraine pain is believed to arise from
activation of the trigeminocervical complex in susceptible individuals. Trigeminovascular activation may
provoke and/or arise from release of multiple neurotransmitters including calcitonin gene-related peptide
(CGRP). Activation of the trigeminal system and enhanced CGRP release in the blood are now considered
hallmarks of migraine pathophysiology. One of the common clinical triggers of migraine is neck pain. We have
characterized a rat model of migraine that recapitulates clinical features of the trigeminal cervical convergence
with a “two-hit” strategy. We provoke migraine-like pain by injecting the rats with CFA (Complete Freund
Adjuvant, 1st hit) to cause mild neck inflammation and then apply umbellulone (2nd hit), the major volatile
molecule emitted by “headache trees”, to trigger cephalic pain. Both insults are required to elicit migraine-like
pain, resembling human migraineurs who have increased susceptibility to the migraine triggers when suffering
from neck pain. We will use this model to determine the possible efficacy of OMT in preventing and/or
relieving migraine-like pain as well as to shed insight on the potential underlying mechanisms by which OMT
could provide benefit in treatment of migraine. Trans-species equivalence of the human soft tissue and
articulatory techniques will be used as the relaxation-promoting approach in rats to determine the effects of
OMT on umbellulone-evoked cephalic pain. Compelling preliminary data indicate that multiple application of
OMT can largely inhibit the development of cephalic allodynia triggered by umbellulone. We will further
pursue two specific aims to elucidate the therapeutic window of OMT in a) preventing and b) reversing
“migraine-like” changes including touch hypersensitivity, reduced voluntary wheel-running activity, enhanced
CGRP release in the blood, and activation of trigeminal tissues. The results from these studies are highly
significant because they will provide a strong neurobiological rationale for use of OMT in managing migraine.
