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

Neurogenic inflammation is known to induce lowering of interstitial fluid pressure ([P.sub.if]) in mouse skin. This study examined the possible role of mast cell activation secondary to neuropeptide release in lowering of [P.sub.if] by using [Kit.sup.w]/ [Kit.sup.w-v] mice, which are devoid of mast cells, including connective tissue mast cells (CTMCs). Pie was measured in paw skin of anesthetized (fentanylfluanison 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 [P.sub.if] in [Kit.sup.w]/[Kit.sup.w-v]`' mice. Intravenous challenge with substance P (SP), calcitonin gene-related peptide (CGRP), or capsaicin induced a significant (P < 0.05) lowering of [P.sub.if] in wild-type mice to -2.16 [+ or -] 0.28, - 1.96 [+ or -] 0.11, and -2.22 [+ or -] 0.19 mmHg, respectively, compared with vehicle (-0.49 [+ or -] 0.11 mmHg). In [Kit.sup.w]/[Kit.sup.w-v] mice the P,- response to SP was completely abolished (-0.53 [+ or -] 0.32 mmHg) while the response to CGRP and capsaicin was attenuated (-1.33 [+ or -] 0.13 and -1.42 [+ or -] 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 [Kit.sup.w]/[Kit.sup.w-v] compared with wild-type mice. We conclude that lowering of [P.sub.if] normally depends on mast cells. However, the sensory nerves can also elicit a lowering of [P.sub.if] that is independent of mast cells. [Kit.sup.w]/[Kit.sup.w-v] mice; neuropeptides; micropuncture