Quantification of Cutaneous Sensory Nerves and Their Substance P Content in Psoriasis

Naukkarinen, Anita; Nickoloff, Brian J.; Farber, Eugene M.

doi:10.1111/1523-1747.ep13071340

Cited by 188 publications

(104 citation statements)

References 27 publications

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“…Investigators have also reported increased levels of neuropeptides and sensory nerves in psoriatic skin lesions, and capsaicin, a chemical that depletes neuropeptides from nerve endings, has been reported to have some therapeutic value in clearing lesions (59,244). Increased concentrations or immunoreactivity for several neuropeptides have been observed in lesional skin of patients with psoriasis (10,154,572,573,643,809). Interestingly, an increase of both VIP-and CGRP-immunoreactive fibers was observed in lesional skin of patients with atopic dermatitis of the "high-stress" group.…”

Section: B Psoriasismentioning

confidence: 99%

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Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Roosterman¹,

Goerge

Schneider

et al. 2006

Physiological Reviews

546

521

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This review focuses on the role of the peripheral nervous system in cutaneous biology and disease. During the last few years, a modern concept of an interactive network between cutaneous nerves, the neuroendocrine axis, and the immune system has been established. We learned that neurocutaneous interactions influence a variety of physiological and pathophysiological functions, including cell growth, immunity, inflammation, pruritus, and wound healing. This interaction is mediated by primary afferent as well as autonomic nerves, which release neuromediators and activate specific receptors on many target cells in the skin. A dense network of sensory nerves releases neuropeptides, thereby modulating inflammation, cell growth, and the immune responses in the skin. Neurotrophic factors, in addition to regulating nerve growth, participate in many properties of skin function. The skin expresses a variety of neurohormone receptors coupled to heterotrimeric G proteins that are tightly involved in skin homeostasis and inflammation. This neurohormone-receptor interaction is modulated by endopeptidases, which are able to terminate neuropeptide-induced inflammatory or immune responses. Neuronal proteinase-activated receptors or transient receptor potential ion channels are recently described receptors that may have been important in regulating neurogenic inflammation, pain, and pruritus. Together, a close multidirectional interaction between neuromediators, high-affinity receptors, and regulatory proteases is critically involved to maintain tissue integrity and regulate inflammatory responses in the skin. A deeper understanding of cutaneous neuroimmunoendocrinology may help to develop new strategies for the treatment of several skin diseases.

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Section: B Psoriasismentioning

confidence: 99%

“…A neurogenic component for the pathophysiology of psoriasis is suggested both by clinical and experimental studies (59,244,572,573). Clinically, psoriatic lesions often have a symmetrical distribution in regions that are traumatized.…”

Section: B Psoriasismentioning

confidence: 99%

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Roosterman¹,

Goerge

Schneider

et al. 2006

Physiological Reviews

546

521

View full text Add to dashboard Cite

show abstract

“…However, it appears that the amount of neuropeptides in normal skin is not suYcient for inducing marked mast cell activation, a conclusion based on the Wndings that capsaicin can induce only weak, if any, histamine release in skin ex vivo and in situ [71,184]. Nevertheless, the case is diVerent in chronic skin inXammation, since increased SP-positive nerve Wbers [128] and increased tissue levels of SP and VIP [36] have been measured in the psoriatic lesion, though there are reports showing only increased VIP levels in the lesional skin [5,149]. Accordingly, topical capsaicin cream has been reported to be eVective in the treatment of psoriatic plaques [9] and the mechanism for this beneWcial eVect may be that prolonged capsaicin treatment depletes neuropeptides from nerves [178].…”

Section: Interactions Between Mast Cells and Sensory Nerves In Psoriasismentioning

confidence: 99%

Is there a role for mast cells in psoriasis?

et al. 2008

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Mast cells have traditionally been considered as eVector cells in allergy but during the last decade it has been realized that mast cells are essentially involved in the mechanisms of innate and acquired immunity. Upon activation by anaphylactic, piecemeal degranulation or degranulation-independent mechanisms mast cells can secrete rapidly or slowly a number of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express cell surface co-stimulatory receptors and ligands, and they can express MHC class II molecules and thereby present antigens. These soluble factors and cell surface molecules can interact with other cells, such as endothelial cells, keratinocytes, sensory nerves, neutrophils, T cell subsets and antigen presenting cells which are essential eVectors in the development of skin inXammation. Besides promoting inXammation, mast cells may attempt in some circumstances to suppress the inXammation and epidermal growth but the regulation between suppressive and proinXammatory mechanisms is unclear. Psoriasis is characterized by epidermal hyperplasia and chronic inXammation where tryptase-and chymase-positive MC TC mast cells are activated early in the developing lesion and later the cells increase in number in the upper dermis with concomitant expression of cytokines and TNF superfamily ligands as well as increased contacts with neuropeptide-containing sensory nerves. Due to the intimate involvement of mast cells in immunity and chronic inXammation the role of mast cells in psoriasis is discussed in this review.

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“…An important role of neurogenic inflammation in the pathogenesis of psoriasis is substantiated by a number of observations 4 -12 : exacerbations during periods of stress, 4 marked proliferation of terminal cutaneous nerves, 6,7 upregulation of neuropeptides [substance P (SP), vasoactive intestinal peptide, calcitonin gene-related peptide (CGRP)] 6 -8 in the psoriatic plaques, therapeutic response to neuropeptide-modulating agents such as capsaicin, 9 soSupported by the Psoriasis Research Institute.…”

mentioning

confidence: 99%

Revisiting the Koebner Phenomenon

Raychaudhuri

Jiang

Raychaudhuri

2008

The American Journal of Pathology

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Nerve growth factor (NGF) influences the key pathological events of psoriasis: keratinocyte proliferation, angiogenesis, and T-cell activation. We have systematically examined the kinetics of NGF expression, keratinocyte proliferation, and migration of T lymphocytes in the epidermis in Koebner-induced developing psoriatic plaques. In skin traumatized by the tape-stripping method (n ‫؍‬ 12), a marked up-regulation of NGF in Koebner-positive lesions (n ‫؍‬ 7) was observed 24 hours after trauma. Synthesis of NGF reached its maximum level in the 2nd week. Furthermore, cultured keratinocytes from nonlesional skin of psoriasis patients produced 10 times higher levels of NGF compared with keratinocytes from healthy individuals. To substantiate the in vivo effect of NGF secreted by keratinocytes in psoriatic plaques, we studied psoriatic plaques and normal human skin in a SCID-human skin xenograft model. The transplanted psoriatic plaques demonstrated marked proliferation of NGF-R (p75)-positive nerve fibers compared with only a few nerves in the transplanted normal human skin. Our results demonstrate that 1) in a developing psoriatic lesion, up-regulation of NGF together with keratinocyte proliferation are early events and precede epidermotropism of T lymphocytes; 2) keratinocytes in patients with psoriasis are primed to produce elevated levels of NGF; and 3) NGF synthesized by these keratinocytes is functionally active.

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Quantification of Cutaneous Sensory Nerves and Their Substance P Content in Psoriasis

Cited by 188 publications

References 27 publications

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Is there a role for mast cells in psoriasis?

Revisiting the Koebner Phenomenon

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