Migraine is a neurovascular disorder that induces debilitating
headaches associated with multiple symptoms including facial
allodynia, characterized by heightened responsivity to normally innocuous mechanical stimuli. It is now well accepted that immune activation and immune-derived inflammatory mediators enhance
pain responsivity, including the trigeminal system.
Nociceptive ("pain" responsive) trigeminal nerves densely innervate the cranial meninges. We have recently proposed that the meninges may serve as a previously unidentified, key interface between the peripheral immune system and the CNS with potential implications for understanding underlying
migraine mechanisms. Our focus here is the development of a model for facial
allodynia associated with
migraine. We developed a model wherein an
indwelling catheter is placed between the skull and dura, allowing immunogenic stimuli to be administered over the dura in awake and freely moving rats. Since the
catheter does not contact the brain itself, any proinflammatory
cytokines induced following manipulation derive from resident or recruited meningeal immune cells. While surgery alone does not alter immune activation markers, TNF or
IL6 mRNA and/or
protein, it does decrease gene expression and increase
protein expression of
IL-1 at 4 days after surgery. Using this model we show the induction of facial
allodynia in response to supradural administration of either the HIV
glycoprotein gp120 or inflammatory soup (
bradykinin,
histamine,
serotonin, and
prostaglandin E2), and the induction of hindpaw
allodynia in our model after inflammatory soup. This model allows time- and dose-dependent assessment of the relationship between changes in meningeal
inflammation and corresponding exaggerated
pain behaviors.