Long-term superior cervical sympathectomy induces mast cell hyperplasia and increases histamine and serotonin content in the rat dura mater

Abstract

Nerve fibres and mast cells are often described in close morphological and functional interactions in various organs such as the dura mater. The respective roles of mast cell activation and sympathetic impairment in cluster headache and migraine attacks have been repeatedly suggested. We have thus investigated the long-term effects of sympathectomy on mast cell morphology and content in the rat dura mater. Fifteen to 60 days after either sham, unilateral or bilateral superior cervical ganglionectomy, dura were removed for either histochemical or biochemical analysis. In the first case, they were fixed and mast cell heparin was stained by fluorescein isothiocyanate-conjugated avidin. Microscopic examination was followed by digital acquisitions using a tomographic process to assess mast cell density in the whole depth of the dura mater. Unilateral ganglionectomy induced a progressive and significant increase in mast cell density 15–60 days post-surgery in contralateral hemi-dura and 30 days post-surgery in ipsilateral hemi-dura. This increase was significant in both dura 60 days after bilateral ganglionectomy. Following perfusion with saline, we also examined the content of histamine and serotonin, pre-formed amines stored in mast cell granules. Biochemical analysis of dura serotonin and histamine content using high-pressure liquid chromatography and radioenzymatic assays, respectively, revealed under all conditions a serotonin tissue concentration lower than that of histamine. After sham ganglionectomy, the dura serotonin content increased from 15 to 60 days post-surgery, whereas the histamine content remained stable over the same period. After unilateral ganglionectomy, the histamine content increased progressively and significantly 30–60 days post-surgery in both hemi-dura, whereas the serotonin content became significantly different from that of sham only 60 days post-surgery in the ipsilateral dura. After bilateral ganglionectomy, the histamine level significantly increased in both hemi-dura 15–60 days post-surgery, whereas the serotonin level had significantly increased at 60 days post-surgery. These results clearly demonstrate, for the first time, a long-term trophic effect of sympathetic nerve degeneration on mast cells in the dura mater. Since mast cell activation has been described previously on the painful side of cluster headache patients during attack periods, we propose that the sympathetic impairment reported in these patients could be prominent, directly or indirectly inducing mast cell hyperplasia and changes in amine contents in the tissue concerned.