Neurogenic Protein Extravasation Research Articles

Neurogenic inflammation in human and rodent skin.

The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge about neurogenic inflammation in human skin, including the involvement of mast cells.

Acute Effects of Substance P and Calcitonin Gene-Related Peptide in Human Skin – A Microdialysis Study

Upon activation nociceptors release neuropeptides in the skin provoking vasodilation and plasma protein extravasation in rodents, but only vasodilation in humans. Pivotal peptides in the induction of neurogenic inflammation comprise calcitonin gene-related peptide and substance P, the latter being suggested to act partly via degranulation of mast cells. In this study substance P and calcitonin gene-related peptide-induced vasodilation, protein extravasation, histamine release, and sensory effects were investigated simultaneously in human skin by dermal microdialysis. The vasodilatory prostaglandin E(2) and the mast cell activator codeine served as positive controls. Substance P and calcitonin gene-related peptide applied intradermally via large cut-off plasmapheresis capillaries induced dose-dependent local vasodilation, but only SP provoked protein extravasation in concentrations greater than 10(-9) M. Substance P-induced (10(-8)-10(-6) M) protein extravasation was not accompanied by histamine release and was unaffected by cetirizine (histamine H1 blocker, 200 microg per ml). Only the highest concentration of substance P (10(-5) M) induced significant histamine release. Neither neuropeptide caused any axon reflex erythema or any itch or pain sensation, whereas mast cell degranulation by codeine dose dependently provoked itch, flare, protein extravasation, and histamine release. In human skin calcitonin gene-related peptide and substance P induce vasodilation by a mechanism not involving histamine. No evidence for neuropeptide-induced activation of nociceptors was obtained. Our results suggest that endogenous calcitonin gene-related peptide and substance P have no acute sensory function in human skin. The lack of neurogenic protein extravasation in humans can most probably be attributed to low local concentrations of this neuropeptide still sufficient to exert trophic and immunomodulatory effects (10(-11) M), but too low to induce protein extravasation (10(-8) M) or even mast cell degranulation (10(-5) M). J Invest Dermatol 115:1015-1020 2000

Topical acetyl salicylate and dipyrone attenuate neurogenic protein extravasation in rat skin in vivo

The effect of topically applied acetyl salicylic acid (ASA) and dipyrone on capsaicin-evoked protein extravasation was investigated by dermal microdialysis in rat. After a baseline of 75 min, capsaicin (1%) was applied epicutaneously under occlusion for 75 min above the capillaries. Topical capsaicin stimulation induced neurogenic protein extravasation with a mean increase of protein concentration in the perfusate of 165±27% (mean±SEM; n=15), whereas in sham-stimulated sites protein concentration decreased to 73±7% of the prestimulation value ( n=6). ASA (2–200 mg/ml) and dipyrone (3–300 mg/ml) dose-dependently reduced the capsaicin induced protein extravasation to 118±23% (ASA, 200 mg/ml; n=8) and 72±9% (dipyrone, 300 mg/ml; n=8) of the prestimulation value. ASA and dipyrone antagonized the excitatory effects of capsaicin on skin nociceptors and thus suppressed the neurogenic protein extravasation.

Effects of vagal perineural capsaicin treatment on vagal efferent and airway neurogenic responses in anesthetized rats.

The acute effect of vagal perineural capsaicin treatment (VPCT) on parasympathetic bradycardia and tracheal neurogenic protein extravasation was examined. In nine anesthetized male Wistar rats the effect of VPCT on the bradycardia induced by electrical stimulation of the vagus was examined. In 24 anesthetized male Wistar rats the effect of VPCT on the tracheal protein extravasation induced by the inhalation of capsaicin aerosols was also studied. VPCT did not alter the bradycardia induced by vagal stimulation or the tracheal protein extravasation induced by the inhalation of capsaicin aerosol. The results of these studies further demonstrate the selectivity of perineural capsaicin treatment on vagal sensory nonmyelinated fibers in the rat and indicate that it is a useful tool for examining the role of sensory vagal C-fibers in pulmonary and cardiovascular reflexes and in isolating C-fiber-mediated reflex responses from those mediated by the release of neuropeptides.