No release of histamine and substance P in capsaicin‐induced neurogenic inflammation in intact human skin <i>in vivo:</i> a microdialysis study

Petersen, Lars Jelstrup; Winge, Kristian; Brodin, Ernst; Skov, Per Stahl

doi:10.1111/j.1365-2222.1997.tb01239.x

Cited by 42 publications

(29 citation statements)

References 46 publications

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“…Our results demonstrate that in humans no such interaction seems to exist, because aprepitant neither increases nor inhibits capsaicin-induced vasodilation, whereas CGRP 8-37 clearly decreases the response to capsaicin. This confirms findings by Petersen et al (1997), who could detect neither SP nor histamine release after intradermal capsaicin administration to humans. We therefore suggest that, in humans, SP has no major role in capsaicin-induced vasodilation.…”

Section: Mediators Of Capsaicin-induced Dermal Vasodilation 251supporting

confidence: 80%

Calcitonin Gene-Related Peptide_8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

Schueren

Rogiers²,

Vanmolkot³

et al. 2008

J Pharmacol Exp Ther

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The purpose of this study was to identify the mediators involved in capsaicin-induced vasodilation in the human skin and to evaluate a pharmacodynamic model for the early clinical evaluation of calcitonin gene-related peptide (CGRP) receptor antagonists. Dermal blood flow (DBF) response of the forearm skin to topically applied capsaicin was measured using laser Doppler perfusion imaging in 22 subjects. The effect of intraarterially administered CGRP 8-37 (1200 ng ⅐ min

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Section: Mediators Of Capsaicin-induced Dermal Vasodilation 251supporting

confidence: 80%

Calcitonin Gene-Related Peptide_8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

Schueren

Rogiers²,

Vanmolkot³

et al. 2008

J Pharmacol Exp Ther

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“…Because of the mast cells' content of several inflammatory mediators and their presence in the vicinity of sensory nerve cells, the mast cells are likely to participate in neurogenic inflammation. A number of studies (5,17,24) have suggested a role for mast cells in the development of edema after neuropeptide challenge, but the ability to release histamine on neuropeptide stimulation seems to vary between species and different mast cell types. Nevertheless, activation of mast cells is associated with anaphylaxis in rats (23) and has been shown to lower P if in both the trachea of rats (15) and skin of both rats and mice (12,20).…”

Section: Discussionmentioning

confidence: 99%

Neurogenic inflammation in mice deficient in heparin-synthesizing enzyme

Karlsen

Iversen²,

Forsberg³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Mast cell activation, or neurogenic inflammation, is known to induce lowering of interstitial fluid pressure (P if) and plasma protein extravasation (PPE) in several tissues from both rats and mice. To examine a possible role of connective tissue mast cells (CTMCs) in these inflammatory responses, we used mice with dysfunctional CTMCs due to lack of the N-deacetylase/N-sulfotransferase-2 enzyme (NDST-2 Ϫ/Ϫ ). Pif and PPE were measured after challenge with compound 48/80 (C48/80), and P if alone was measured after treatment either with capsaicin, substance P (SP), or calcitonin gene-related peptide (CGRP). Measurements of P if in anesthetized (fentanyl/fluanison and midazolam, 1:1) mice were performed in paw skin with glass capillaries connected to a servo-controlled counterpressure system. PPE was measured with microdialysis by using hollow plasmapheresis fibers (cutoff at 3,000 kDa) placed subcutaneously on the back. Intravenous administration of C48/80 lowered P if significantly (P Ͻ 0.05) in NDST-2 Ϫ/Ϫ mice (Ϫ1.67 Ϯ 0.42 mmHg) compared with vehicle (Ϫ0.57 Ϯ 0.17 mmHg) but the lowering was significantly (P Ͻ 0.05) less compared with that of the NDST-2 ϩ/ϩ mice (Ϫ2.31 Ϯ 0.47 mmHg). PPE was increased 300% after treatment with C48/80 in NDST-2 ϩ/ϩ mice, whereas there was no increase in PPE in NDST-2 Ϫ/Ϫ mice. Capsaicin, SP, and CGRP lowered P if significantly (P Ͻ 0.05) compared with vehicle and to the same extent in both NDST-2 ϩ/ϩ and NDST-2 Ϫ/Ϫ mice. We can conclude that although NDST-2 Ϫ/Ϫ mice demonstrate an altered response in P if after mast cell activation, there was no similar alteration after neurogenic inflammation. Therefore, we suggest that neurogenic inflammation in mouse skin is not exclusively dependent on intact CTMCs. N-deacetylase/N-sulfotransferase-2; mast cell; capsaicin; peptides; micropuncture INTERSTITIAL FLUID PRESSURE (P if ) is important in the control of interstitial fluid balance. Under normal conditions, there is a fine-tuned balance between fluid entering the interstitium from the surrounding capillaries and fluid leaving through the lymphatics, thus preventing accumulation of excess fluid. Factors interacting in the control of transcapillary fluid flux (J v ) are the product of the capillary filtration coefficient (CFC) and the difference between the hydrostatic pressure (P) and the colloid osmotic pressure (COP) across the capillary. This interaction of forces is expressed in the Starling equation:, where c and if denote the capillary and the interstitial fluid, respectively, and is the capillary reflection coefficient for proteins. P if has a dual role in the control of interstitial fluid balance. Under normal conditions, excess fluid filtered over the capillaries would increase P if and reduce COP if and hence oppose further fluid filtration and prevent the formation of edema in a passive manner (1). P if is also the filling pressure for the initial lymphatics and an increase in P if will thus increase lymph flow (1). However, contrary to the situation in normal control of inte...

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“…Supporting the involvement of mast cells are the findings that stimulation of the rat saphenous nerve induces mast cell degranulation (27) and that SP in high concentrations (40) as well as topical application of capsaicin (7) induce cutaneous mast cell degranulation in human forearm. In contrast, Petersen et al (32) detected no release of SP and histamine after capsaicin injection in the same area.…”

mentioning

confidence: 88%

“…Although mast cells express SP receptors, their involvement in neurogenic inflammation has been debated. Neuropeptides can induce histamine release in a number of tissues (12,13,23,29), but it has been questioned whether endogenously released neuropeptides are present in sufficient amounts to induce mast cell activation and subsequent histamine release in human skin (22,32,40).…”

Section: Discussionmentioning

confidence: 99%

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

Karlsen¹,

Bletsa²,

Gjerde³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Neurogenic inflammation is known to induce lowering of interstitial fluid pressure (P if) in mouse skin. This study examined the possible role of mast cell activation secondary to neuropeptide release in lowering of P if by using , and neurokinin A, from the capsaicin-sensitive nerve endings. Capsaicin releases neuropeptides through binding to the vanilloid receptor subtype 1 (VR1) (9), which in turn induces an inflammatory response in various tissues of both rodents and humans (2, 21). This response is characterized by increased arteriolar vasodilatation and protein extravasation due to increased permeability of the postcapillary venules resulting in fluid accumulation in the tissue. Previous reports from our research group have shown that the response in the initial phase of neurogenic inflammation involves lowering of interstitial fluid pressure (P if ) as observed both in rat trachea (16) and mouse skin (25). P if is important in tissue fluid homeostasis both in the regulation of fluid filtration across the capillary and as the filling pressure for the lymphatics (1). In contrast to the classic view of P if serving as an edema-preventing mechanism, P if has been shown to play an active part in the initial phase of edema in a number of inflammatory models with a lowering of P if to more negative values (16,31,34,35). According to Starling's hypothesis, this lowering of P if will increase net filtration pressure across the capillary and hence contribute to fluid accumulation in the interstitial space.Mast cells have been thought of as possible participants in the neurogenic inflammatory response because they contain numerous inflammatory mediators and are localized in close proximity to the capsaicin-sensitive nerve endings (37,39). Alterations in the number of SP-reactive fibers and mast cell-nerve contacts have been reported as parts of the pathology of several diseases (3,19,45). SP can activate mast cells both through binding of the neurokinin-1 receptor present on these cells (8) and through receptor-independent mechanisms (10). The significance of mast cell activation as a part of neurogenic inflammation has been questioned in a number of studies, and the results are yet not conclusive. Supporting the involvement of mast cells are the findings that stimulation of the rat saphenous nerve induces mast cell degranulation (27) and that SP in high concentrations (40) as well as topical application of capsaicin (7) induce cutaneous mast cell degranulation in human forearm. In contrast, Petersen et al. (32) detected no release of SP and histamine after capsaicin injection in the same area.In light of the knowledge that capsaicin-sensitive nerve endings are localized close to connective tissue mast cells (CTMCs) in mouse skin (6) and that mast cell activation by compound 48/80 (C48/80) induces a lowering of P if in skin of both rats and mice (20,25,36), the question arises as to whether mast cells are involved in the events leading to lowering of P if in neurogenic inflammation. In a recent study (25) we exami...

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No release of histamine and substance P in capsaicin‐induced neurogenic inflammation in intact human skin in vivo: a microdialysis study

Abstract: Capsaicin-induced neurogenic activation does not involve the release of histamine from mast cells or detectable amounts of substance P release from sensory nerves in normal human skin in vivo.

Cited by 42 publications

References 46 publications

Calcitonin Gene-Related Peptide_8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

Calcitonin Gene-Related Peptide_8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

Neurogenic inflammation in mice deficient in heparin-synthesizing enzyme

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

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No release of histamine and substance P in capsaicin‐induced neurogenic inflammation in intact human skin in vivo: a microdialysis study

Abstract: Capsaicin-induced neurogenic activation does not involve the release of histamine from mast cells or detectable amounts of substance P release from sensory nerves in normal human skin in vivo.

Cited by 42 publications

References 46 publications

Calcitonin Gene-Related Peptide8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

Calcitonin Gene-Related Peptide8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

Neurogenic inflammation in mice deficient in heparin-synthesizing enzyme

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

Contact Info

Product

Resources

About

Calcitonin Gene-Related Peptide_8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

Calcitonin Gene-Related Peptide_8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model