Morphological and functional demonstration of rat dura mater mast cell-neuron interactions in vitro and in vivo

Mast cells derive from a distinct bone marrow precursor and mature in tissu es under the influence of stem cell factor, nerve growth factor (NGF) and c ertain interleukins. Intracranial mast cells first appear in the meninges a nd are located perivascularly close to neurons. They can be activated by an tidromic stimulation of the trigeminal nerve, as well as by acute immobiliz ation stress. Substance P (SP) and corticotropin-releasing hormone (CRH) ar e particularly potent in stimulating mast cell release of vasoactive, infla mmatory and nociceptive molecules. These findings have suggested that mast cells may be involved in neuroinflammatory conditions, such as migraines. I n this study, dura mast cells were shown to have characteristics of connect ive tissue mast cells (CTMC) as they contained histamine, heparin and rat m ast cell protease I (RMCP-I). Mast cells were localized close to SP-positiv e neurons immunocytochemically and mast cell-neuron contacts were also docu mented using scanning electron microscopy. Dura stimulated by SP and carbac hol in situ released histamine. Preincubation of dura with estradiol slight ly augmented histamine release by SP, an effect possibly mediated through e strogen receptors identified on dura mast cells. Acute stress by immobiliza tion led to dura mast cell degranulation which was prevented by pretreatmen t with a neutralizing antibody to CRH or a CRH receptor antagonist. The pre sent results further clarify the biology of intracranial mast cells and sup port their involvement in the pathophysiology of migraines which are precip itated or worsened by stress. (C) 1999 Elsevier Science B.V. All rights res erved.