STRESS-INDUCED INTRACRANIAL MAST-CELL DEGRANULATION - A CORTICOTROPIN-RELEASING HORMONE-MEDIATED EFFECT

Stress is known to precipitate or worsen a number of disorders, such a s migraines, in which mast cells are suspected of being involved by re leasing vasoactive, nociceptive, and proinflammatory mediators. Howeve r, no functional association has been demonstrated yet between a migra ine trigger and brain mast cell activation. Nontraumatic immobilizatio n (restrain) stress has been shown to stimulate the hypothalamic-pitui tary-adrenal axis and to cause redistribution of immune cells. Here,re strain stress caused degranulation in 70% of rat dura mast cells withi n 30 min, as shown both by light and electron microscopy. These morpho logic findings were accompanied by cerebrospinal fluid elevation of ra t mast cell protease I, but not II, indicating secretion from connecti ve tissue type mast cells. Mast cell activation due to stress was abol ished in animals that had been treated neonatally with capsaicin, indi cating that neuropeptides in sensory nerve endings are involved in thi s response. Complete inhibition was also achieved by pretreating the a nimals ip with polyclonal antiserum to CRH. Mast cells in the dura wer e localized close to nerve processes containing substance P, but no CR H-positive fibers were identified even though these were found close t o mast cells in the median eminence. This is the first time that stres s is shown to activate intracranial mast cells, apparently through the sequential action of CRH and sensory neuropeptides. These findings ma y have implications for the pathophysiology and possible therapy of ne uroinflammatory disorders such as migraines, which are induced or exac erbated by stress.