Lowering of interstitial fluid pressure after neurogenic inflammation in mouse skin is partly dependent on mast cells

Abstract

Neurogenic inflammation is known to induce lowering of interstitial fluid pressure (Pif) in mouse skin. This study examined the possible role of mast cell activation secondary to neuropeptide release in lowering of Pifby using KitW/ KitW-vmice, which are devoid of mast cells, including connective tissue mast cells (CTMCs). Pifwas measured in paw skin of anesthetized (fentanyl-fluanison and midazolam, 1:1) mice with glass capillaries connected to a servo-controlled counterpressure system. In contrast to wild-type mice, intravenous administration of mast cell-activating compound 48/80 induced no lowering of Pifin KitW/ KitW-vmice. Intravenous challenge with substance P (SP), calcitonin gene-related peptide (CGRP), or capsaicin induced a significant ( P < 0.05) lowering of Pifin wild-type mice to −2.16 ± 0.28, −1.96 ± 0.11, and −2.22 ± 0.19 mmHg, respectively, compared with vehicle (−0.49 ± 0.11 mmHg). In KitW/ KitW-vmice the Pifresponse to SP was completely abolished (−0.53 ± 0.32 mmHg) while the response to CGRP and capsaicin was attenuated (−1.33 ± 0.13 and −1.42 ± 0.13 mmHg, respectively) although significantly ( P < 0.05) lowered compared with vehicle. Immunohistochemical analysis revealed no difference in distribution or density of SP- and CGRP-immunoreactive fibers in paws of KitW/ KitW-vcompared with wild-type mice. We conclude that lowering of Pifnormally depends on mast cells. However, the sensory nerves can also elicit a lowering of Pifthat is independent of mast cells.