Neuropeptides concentrations in the skin of a murine (NC/Nga mice) model of atopic dermatitis

Katsuno, Masako; Aihara, Michiko; Kojima, Masako; Osuna, Hiroyuki; Hosoi, Junichi; Nakamura, Motokazu; Toyoda, Masahiko; Matsuda, Hiroshi; Ikezawa, Zenrō

doi:10.1016/s0923-1811(03)00155-5

Cited by 35 publications

(33 citation statements)

References 29 publications

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“…The role of substance P in heat is more contradictory; Zimmer et al (1998) have shown that disruption of substance P signaling through genetic ablation of the tachykinin-1 gene results in longer response latencies in the hotplate test, whereas the behavioral response to the tail flick was unaffected. However, genetic disruption of the substance P receptor gene did not result in any differences in acute heat pain (De Felipe et al, 1998;Zimmer et al, 1998), which is consistent with our findings that substance P is not required for heat pain transmission.…”

Section: Discussionsupporting

confidence: 92%

“…The selectivity of the drugs is another potential confounding factor. However, BIBN4096BS does not have any relevant affinity for a set of 75 different receptors or enzyme systems (Doods et al, 2000). Similarly, Win51708 was tested both pharmacologically and biochemically for its selective action on the substance P system (Venepalli et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Multimodal Use of Calcitonin Gene-Related Peptide and Substance P in Itch and Acute Pain Uncovered by the Elimination of Vesicular Glutamate Transporter 2 from Transient Receptor Potential Cation Channel Subfamily V Member 1 Neurons

et al. 2014

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Primary afferents are known to use glutamate as their principal fast neurotransmitter. However, it has become increasingly clear that peptides have an influential role in both mediating and modulating sensory transmission. Here we describe the transmission accounting for different acute pain states and itch transmitted via the transient receptor potential cation channel subfamily V member 1 (TRPV1) population by either ablating Trpv1-Cre-expressing neurons or inducing vesicular glutamate transporter 2 (VGLUT2) deficiency in Trpv1-Cre-expressing neurons. Furthermore, by pharmacological inhibition of substance P or calcitonin gene-related peptide (CGRP) signaling in Vglut2-deficient mice, we evaluated the contribution of substance P or CGRP to these sensory modulations, with or without the presence of VGLUT2-mediated glutamatergic transmission in Trpv1-Cre neurons. This examination, together with c-Fos analyses, showed that glutamate via VGLUT2 in the Trpv1-Cre population together with substance P mediate acute cold pain, whereas glutamate together with CGRP mediate noxious heat. Moreover, we demonstrate that glutamate together with both substance P and CGRP mediate tissue-injury associated pain. We further show that itch, regulated by the VGLUT2-mediated transmission via the Trpv1-Cre population, depends on CGRP and gastrin-releasing peptide receptor (GRPR) transmission because pharmacological blockade of the CGRP or GRPR pathway, or genetic ablation of Grpr, led to a drastically attenuated itch. Our study reveals how different neurotransmitters combined can cooperate with each other to transmit or regulate various acute sensations, including itch.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Multimodal Use of Calcitonin Gene-Related Peptide and Substance P in Itch and Acute Pain Uncovered by the Elimination of Vesicular Glutamate Transporter 2 from Transient Receptor Potential Cation Channel Subfamily V Member 1 Neurons

et al. 2014

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“…Other mediators, such as substance P, are believed to play important roles in the symptoms observed in NC / Nga mice and humans. Substance P is reported to play an important role in the pathogenesis of human atopic dermatitis (16,40,41), and some authors have suggested using in vivo models (42,43).…”

Section: Discussionmentioning

confidence: 99%

Effects of Anti-Nerve Growth Factor Antibody on Symptoms in the NC/Nga Mouse, an Atopic Dermatitis Model

2005

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Abstract. Nerve growth factor (NGF) is an important substance in the skin, where it can modulate nerve maintenance and repair. However, the direct link between NGF and pruritic disease such as atopic dermatitis is not yet fully understood. To determine whether NGF plays a major role in atopic dermatitis and in the development or maintenance of skin lesions, we performed a study using NC / Nga mice and compared mice with and without skin lesions. Our examinations of the NC / Nga mice sought to detect nerve fibers in the epidermis, measured serum and skin NGF content, and observed skin NGF by immunohistochemistry staining. We also examined the effects of anti-NGF antibody on dermatitis symptoms in NC / Nga mice. In these mice, nerve fibers were significantly increased in the epidermis of lesioned skin, and the NGF content of the serum and skin was significantly elevated. Anti-NGF antibodies significantly inhibited the development and proliferation of skin lesions and epidermal innervation and significantly inhibited any growth in scratching but did not ameliorate scratching already developed. Our findings suggest that NGF plays important roles in the pathogenesis of atopic dermatitis-like skin lesions and that inhibiting the physiological effects of NGF or suppressing increased NGF production may prevent or even moderate the symptoms of atopic dermatitis.

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“…For instance, sensory nerve fibers are immunoreactive for SP and CGRP (761), SP and PACAP (549), or CGRP and SST (76). However, the factors that determine the relative concentration of these neuropeptides in different nerve fibers of the skin are not well understood, although distinct regulatory functions of neuropeptide-neuropeptide interactions have been observed (33,418).…”

Section: B Cutaneous Neuropeptides and Neuropeptide Receptor Biologymentioning

confidence: 99%

“…In acute as well as lichenified lesions of atopic dermatitis, increased staining of cutaneous nerves or concentrations of neuropeptides was observed (265, 299,377,418,609,642,826,874,886). Furthermore, characteristics of the triple response (erythema, wheal, flare) of "neurogenic inflammation" as well as pruritus have been observed after injection of neuropeptides into human skin (333,335).…”

Section: Atopic Dermatitismentioning

confidence: 99%

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

Roosterman¹,

Goerge

Schneider

et al. 2006

Physiological Reviews

556

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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Neuropeptides concentrations in the skin of a murine (NC/Nga mice) model of atopic dermatitis

Cited by 35 publications

References 29 publications

Multimodal Use of Calcitonin Gene-Related Peptide and Substance P in Itch and Acute Pain Uncovered by the Elimination of Vesicular Glutamate Transporter 2 from Transient Receptor Potential Cation Channel Subfamily V Member 1 Neurons

Multimodal Use of Calcitonin Gene-Related Peptide and Substance P in Itch and Acute Pain Uncovered by the Elimination of Vesicular Glutamate Transporter 2 from Transient Receptor Potential Cation Channel Subfamily V Member 1 Neurons

Effects of Anti-Nerve Growth Factor Antibody on Symptoms in the NC/Nga Mouse, an Atopic Dermatitis Model

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

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