Neurophysiology of Pruritus

Ständer, Sonja; Steinhoff, Martin; Schmelz, Martin; Weißhaar, Elke; Metze, Dieter; Luger, Thomas A.

doi:10.1001/archderm.139.11.1463

Cited by 193 publications

(31 citation statements)

References 92 publications

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“…Using confocal imaging microscopy, we could demonstrate that µ-opiate receptors are not only expressed in keratinocytes but also on unmyelinated peripheral nerve fibers in the dermis and epidermis [2]. These results are confirmed by other research groups [5, 6]. Some of the peripheral nerve fibers also express the ligand β-endorphin.…”

Section: Introductionsupporting

confidence: 73%

Changes of Epidermal Mu-Opiate Receptor Expression and Nerve Endings in Chronic Atopic Dermatitis

et al. 2005

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There is increasing evidence that neuropeptides such as a substance P, neurotrophins or β-endorphin, an endogenous agonist for µ-opioid receptor, are involved in the pathogenesis of atopic dermatitis in which mental stress and scratching deteriorate the disease. µ-Opioid receptor, a G-protein-coupled receptor, can be downregulated and internalized by agonists and other factors in vitro. In this study, we investigated the regulation of µ-opioid receptor and nerve endings in atopic dermatitis patients. Skin biopsies from atopic dermatitis patients revealed a significant downregulation of µ-opiate receptor expression in epidermis of atopic dermatitis. Permeabilization of the skin showed that the receptor in keratinocytes from atopic dermatitis is internalized. The mRNA expression pattern of the µ-opiate receptor is different in epidermis taken from patients with chronic atopic dermatitis compared to normal skin. In atopic dermatitis, the mRNA is concentrated in the subcorneal layers of the epidermis and in normal skin in the suprabasal layers. Staining of the nerve endings using protein gene product 9.5 shows a different pattern of epidermal nerve endings in normal skin compared to atopic dermatitis. In normal skin, the epidermal nerve endings are rather thick. However, in atopic dermatitis, the epidermal nerve endings are thin and run straight through the epidermis. Based on these observations and combining the ‘intensity’ and ‘pattern’ hypothesis, we propose a new theory especially for histamine-unrelated, peripheral induction of chronic pruritus. We suggest that ‘itch’ is elicited in the epidermal unmyelinated nerve C-fibers and ‘pain’ in the dermal unmyelinated nerve fibers. The downregulation of the opioid receptor in the epidermis contributes to the chronic itching. We call this new hypothesis the ‘layer hypothesis’.

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Section: Introductionsupporting

confidence: 73%

Changes of Epidermal Mu-Opiate Receptor Expression and Nerve Endings in Chronic Atopic Dermatitis

et al. 2005

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“…Both central and peripheral mediators are important in the etiology of pruritus. Specifically, histamine, proteinase, substance P, neurotrophin, prostanoids, and interleukins are all compounds believed to play a role in peripherally mediated pruritis14. Emerging research suggests that many additional intrinsic biochemical compounds may also contribute to pruritis in AD patients.…”

Section: Discussionmentioning

confidence: 99%

IL-31 Serum Protein and Tissue mRNA Levels in Patients with Atopic Dermatitis

Kim

Yang

et al. 2011

Ann Dermatol

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BackgroundSevere pruritus is the primary symptom in atopic dermatitis (AD). Recently, the novel cytokine IL-31 has been implicated in the itching associated with AD.ObjectiveWe performed this study to determine whether IL-31 serum levels are elevated in AD patients and to better characterize the relationship between serum IL-31 level and other established laboratory parameters.MethodsWe recruited 55 AD patients, 34 with allergic type AD and 21 with non-allergic type AD, and 38 healthy, non-atopic controls. We checked the laboratory values, severity score, and serum IL-31 levels in all patients and controls, and IL-31 mRNA levels in lesion skin were measured in 13 subjects with AD and in four controls.ResultsAD patients displayed significantly higher levels of serum IL-31 that were associated with serum IgE, disease severity, and subjective itch intensity. In AD patients, IL-31 mRNA levels from the lesional skin samples also correlated with serum IL-31 level.ConclusionIL-31 is likely one of the many mediators inducing inflammation and pruritus in AD. Although our limited sample size prevents us from making any definitive conclusions, our data demonstrate a strong correlation between IL-31 mRNA level and serum IL-31 protein level, which has never been reported before. Moreover, we found correlations between serum IL-31 level and serum IgE, eosinophil cationic protein, disease severity, and subject itch intensity in certain degrees in AD patients.

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“…That published reviews, original articles and even textbooks on the subject of itch are becoming more plentiful of late [1, 2, 3, 4]encourages the hope that this Cinderella of neuro- and skin physiology is at last beginning to receive the attention that it deserves.…”

Section: Introductionmentioning

confidence: 99%

Itch: More than Skin Deep

Greaves

Khalifa

2004

Int Arch Allergy Immunol

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Recent research in neurophysiology of itch has indicated the existence of itch-dedicated nociceptor neurones. The perception of itch is regulated by tonically inhibitory descending neuronal pathways and nociceptor spinal neuronal circuits. There is at present no convincing evidence of an ‘itch centre’ in the brain. A classification of itch has been proposed, based on neurophysiological considerations, which stresses the importance of neurogenic and neuropathic itch, and assists in differential diagnosis and selection of treatment. However, more than one class of itch can occur concurrently in the same patient. The importance of cross- talk between dermal mast cells and nociceptor nerve terminals, involving cleavage of proteinase-activated receptor 2 by mast cell tryptase, is highlighted. The pruritus of cholestasis is mediated at least in part by opioid peptides synthesized by the liver, and elevated levels of these mediators are found in the plasma and skin of patients with itch due to cholestasis. The combined use of both µ- receptor antagonists and ĸ-receptor agonists (anti-pruritic) is worth exploring.

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Neurophysiology of Pruritus

Cited by 193 publications

References 92 publications

Changes of Epidermal Mu-Opiate Receptor Expression and Nerve Endings in Chronic Atopic Dermatitis

Changes of Epidermal Mu-Opiate Receptor Expression and Nerve Endings in Chronic Atopic Dermatitis

IL-31 Serum Protein and Tissue mRNA Levels in Patients with Atopic Dermatitis

Itch: More than Skin Deep

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