FUNCTIONAL-RELATIONSHIPS BETWEEN SENSORY NERVE-FIBERS AND MAST-CELLS OF DURA-MATER IN NORMAL AND INFLAMMATORY CONDITIONS

In this study, we have characterized the phenotype of mast cells in ra t dura mater and their topological and functional relationships with C -fibers in normal and inflammatory conditions. Three mast cell populat ions with different size, morphology and localization were characteriz ed by their content of specific neutral serine proteases. They showed immunoreactivity corresponding to rat mast cell protease I, rat mast c ell protease II, or both proteases. Using confocal microscopy, all thr ee mast cell types were observed in close apposition (distance less th an 100 nm) to calcitonin gene-related peptide- and substance P-immunor eactive nerve fibers in both controls and rats infected with the nemat ode Nippostrongylus brasiliensis. After nematode infection or neonatal treatment with capsaicin, a large increase in the number of rat mast cell protease II-immunoreactive mast cells was found within dura mater segments (+1478% and +596%, respectively), without concomitant change s of rat mast cell protease I- or rat mast cell protease I/II-immunore active mast cells. Under both these conditions, the increase in mast c ell number was accompanied by a significant increase in rat mast cell protease II level within tissue extracts (+281% after nematode infecti on and +36% after capsaicin treatment). The functional interaction of mast cells with sensory nerve fibers in the dura mater was assessed by evaluating [H-3]histamine synthesis after administration of L-[H-3]hi stidine, an index of mast cell activity. The H-3 receptor agonist (R)- alpha-methylhistamine (15 mg/kg, i.p.) had no effect, but administrati on of the II, receptor antagonist, thioperamide (10 mg/kg, i.p.), resu lted in a significant increase of [H-3]histamine synthesis (+62%). Thi s effect was reduced in neonatal capsaicin-treated rats, but not compl etely suppressed (+35%), very likely because of partial denervation, a s assessed by monitoring calcitonin gene-related peptide immunoreactiv ity. It is concluded that, in the dura mater, as in peripheral tissues , sensory nerve fibers and mast cells actively synthesizing and releas ing histamine form a short inhibitory feedback loop involving prejunct ional H-3-receptors that could regulate the release of pro-inflammator y mediators, thus limiting the extent of inflammatory reactions. (C) 1 997 IBRO.