The Role of Proteolytic Enzymes in the Production of Pruritus in Man*

Arthur, Robert P.; Shelley, Walter B.

doi:10.1038/jid.1955.138

Cited by 66 publications

(20 citation statements)

References 11 publications

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“…Arthur & Shelley conducted a comprehensive study, administering numerous proteases by means of inert cowhage spicules and intradermal injections. Here, papain was found to be the most effective itch inducer of 48 tested enzymatic substances (63). More recently, papain administered by intra-cutaneous injection was shown to produce highly variable responses, i.e.…”

Section: Proteinase-activated Receptor 2/4 (Par) Mediated Itchmentioning

confidence: 98%

Human Surrogate Models of Histaminergic and Non-histaminergic Itch

Andersen¹,

Elberling²,

Arendt-Nielsen³

2014

Acta Derm Venerol

110

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Within the last decade understanding of the mechanistic basis of itch has improved significantly, resulting in the development of several human surrogate models of itch and related dysesthetic states. Well-characterized somatosensory models are useful in basic studies in healthy volunteers, in clinical studies for diagnostic and segmentation purposes, and in pharmacological studies to evaluate the antipruritic efficacy of existing and novel compounds. This review outlines recently introduced histamine-independent human models of itch, their mechanisms, their ability to induce clinically relevant phenomena, such as alloknesis, and the results obtained through their use. The article also introduces recent advances in the understanding of itch and provides an overview of the methods to assess experimentally-induced itch and associated manifestations. Major improvements are warranted in the treatment of chronic pruritus, and reliable human surrogate models are a valuable tool in achieving them, both for basic researchers and for clinicians.

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Section: Proteinase-activated Receptor 2/4 (Par) Mediated Itchmentioning

confidence: 98%

Human Surrogate Models of Histaminergic and Non-histaminergic Itch

Andersen¹,

Elberling²,

Arendt-Nielsen³

2014

Acta Derm Venerol

110

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“…Intracutaneous and subcutaneous injections of the pruritogenic substances histamine and papain were used, since these substances have previously been shown to produce itch (Arthur and Shelley, 1955;Shelley and Arthur, 1957; Hagermark, 1974; Fjellner and Hagermark, 1981; Simone et al, 1987; Magerl and Handwerker, 1988). Intracutaneous and subcutaneous injections of the pruritogenic substances histamine and papain were used, since these substances have previously been shown to produce itch (Arthur and Shelley, 1955;Shelley and Arthur, 1957; Hagermark, 1974; Fjellner and Hagermark, 1981; Simone et al, 1987; Magerl and Handwerker, 1988).…”

mentioning

confidence: 99%

Psychophysical Studies of the Itch Sensation and Itchy Skin (“Alloknesis”) Produced by Intracutaneous Injection of Histamine

Simone

Alreja

LaMotte

1991

Somatosensory & Motor Research

177

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Psychophysical measurements of itch and itchy skin ("alloknesis"--itch produced by innocuous mechanical stimulation) were obtained in human volunteers following intracutaneous or subcutaneous injections of histamine or papain into the volar forearm. Histamine and papain were given in doses of 0.1, 1, or 10 micrograms in 10 microliters of saline. The effects of the depth of injection and of skin temperature on the latency, magnitude, and duration of itch were examined. Also, dose-response functions were obtained for the area of alloknesis produced by intracutaneous injections of histamine. Finally, the neural mechanisms underlying the spread of alloknesis were investigated via local anesthesia of the skin. Intracutaneous and subcutaneous injections of histamine, but not papain, produced a sensation of itch without pain. The latency of itch was shorter after an intracutanous than after a subcutaneous injection of histamine. The mean latencies of itch produced by a 1-microgram dose were 9.5 and 23.0 sec for intracutaneous and subcutaneous injections, respectively. No differences were observed in the magnitude or duration of itch. Similarly, the latency of itch was increased when the skin temperature at injection site was lowered to 15 degrees C, whereas the magnitude and duration of itch were unaffected. Intracutaneous and subcutaneous injections of histamine produced similar areas of alloknesis. However, the magnitude and duration of alloknesis were dependent on dose. The mean maximum areas of alloknesis produced by intracutaneous injections of 0.1, 1, and 10 micrograms of histamine were 28.3, 47.2, and 43.8 cm2, respectively. Alloknesis was present at 2 min after injection, increased to a maximum area without 10 min, and then gradually decreased during the next 25-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Further investigations confirmed the biochemical nature of this pruritic agent, identified as a thermolabile protein with a molecular weight of 40 000 (7). Depletion of mast cell histamine prior to the injection of trypsin or chymase markedly abrogated the itch response suggesting a role of trypsin and chymase as histamine liberators (4,6).…”

Section: Proteases Involved In Pruritusmentioning

confidence: 99%

Viewpoint 5

Steinhoff¹,

Roosterman²

2005

Experimental Dermatology

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How best to fight that nasty itch -from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches. Exp Dermatol 2005: 14: 225-240. # Blackwell Munksgaard, 2005 While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach -beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management. Viewpoint 1 Setting:Physiology seminar, Department of Physiology, University of Debrecen, Hungary Teacher:Good morning, Class! As you may all remember, during the previous seminars, we introduced the neurophysiological details of the mechanisms and interactions underlying one of the 'ugliest', yet most fascinating sensory phenomena -itch. Before reviewing your ideas that you collected as your 'home-work' (i.e. How would you best fight that nasty itch?), let me briefly summarize key features of our current understanding of itch.Itch (pruritus) is an unpleasant cutaneous sensation which provokes the desire to scratch (1). Neurophysiologically, itch sensation is initiated by pruritogenic substances that stimulate a subset of specialized skin C-fibers. The latter are distinct from the polymodal C-type neurons which transmit nociceptive (i.e. painful) stimuli to the central nervous system (2). Many endogenous substances are regarded as 'mediators of itch' (3), e.g. amines Experimental Dermatology 2005: 14: 225-240 225(such as histamine), proteases, opioids, lipid peroxidation metabolites (such as leukotrienes, prostaglandins), neuropeptides (e.g. substance P), cytokines, growth factors (e.g. nerve growth factor), and many others (reviewed in 3-5). These agents may either directly stimulate/sensitize the above itch-mediating sensory nerve endings to fire action potentials and to locally release va...

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The Role of Proteolytic Enzymes in the Production of Pruritus in Man*

Cited by 66 publications

References 11 publications

Human Surrogate Models of Histaminergic and Non-histaminergic Itch

Human Surrogate Models of Histaminergic and Non-histaminergic Itch

Psychophysical Studies of the Itch Sensation and Itchy Skin (“Alloknesis”) Produced by Intracutaneous Injection of Histamine

Viewpoint 5

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