Itch: More than Skin Deep

Greaves, Malcolm W.; Khalifa, Nedha

doi:10.1159/000080898

Cited by 59 publications

(46 citation statements)

References 24 publications

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“…This itch reduction is based on a spinal antagonism between pain- and itch-processing neurons (8). This illustrates a therapeutically exploitable, key concept in contemporary pruritus research: itch appears to be under tonic inhibitory control of pain-related signals (1,4,5,8,9). Indeed, itch and pain share the use of many neurophysiological tools and processing centers and induce similar autonomous skin reactions.…”

mentioning

confidence: 86%

Frontiers in pruritus research: scratching the brain for more effective itch therapy

Paus

Schmelz

Bı́ró

et al. 2006

Journal of Clinical Investigation

329

287

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This Review highlights selected frontiers in pruritus research and focuses on recently attained insights into the neurophysiological, neuroimmunological, and neuroendocrine mechanisms underlying skin-derived itch (pruritogenic pruritus), which may affect future antipruritic strategies. Special attention is paid to newly identified itch-specific neuronal pathways in the spinothalamic tract that are distinct from pain pathways and to CNS regions that process peripheral pruritogenic stimuli. In addition, the relation between itch and pain is discussed, with emphasis on how the intimate contacts between these closely related yet distinct sensory phenomena may be exploited therapeutically. Furthermore, newly identified or unduly neglected intracutaneous itch mediators (e.g., endovanilloids, proteases, cannabinoids, opioids, neurotrophins, and cytokines) and relevant receptors (e.g., vanilloid receptor channels and proteinase-activated, cannabinoid, opioid, cytokine, and new histamine receptors) are discussed. In summarizing promising new avenues for managing itch more effectively, we advocate therapeutic approaches that strive for the combination of peripherally active antiinflammatory agents with drugs that counteract chronic central itch sensitization. The study of pruritus in a nutshellItching (pruritus) is perhaps the most common symptom associated with numerous skin diseases and can be a lead symptom of extracutaneous disease (e.g., malignancy, infection, and metabolic disorders) (1, S1). However, despite approximately a century of pruritus research (2, S2, S3), there is no generally accepted therapy for the treatment of itch, and many mysteries, misconceptions, and controversies still haunt this rather neglected, yet clinically important and scientifically fascinating, niche in the life sciences (3, 4, 5). It is the brain that itches, not the skinPruritus causes the desire to scratch the skin and is experienced as a sensation arising in the skin. However, like all other skin sensations, itch, strictly speaking, is an extracutaneous event - a product of CNS activities. The intense itch we feel after an insect bite, in a patch of atopic eczema, during an episode of food-induced urticaria, or in association with diabetes, uremia, or scabies mite infection (S1) represents a neuronal projection of a centrally formed sensation into defined regions of the integument (localized pruritus) or into large territories of our body surface (generalized pruritus).Interestingly, our individual reception of and emotional response to itch strongly depends on its exact quality: while a tickling sensation usually is experienced as pleasurable, persistent itch is an annoying or even torturous sensation (S4). While one is tempted to interpret this as indicating a distinct molecular and/or structural basis of these different itch qualities, it has proven excruciatingly difficult to identify their molecular, structural, and neurophysiological differences (ref. 1; see below).As pruritus can arise from localized or systemic, peripheral o...

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mentioning

confidence: 86%

Frontiers in pruritus research: scratching the brain for more effective itch therapy

Paus

Schmelz

Bı́ró

et al. 2006

Journal of Clinical Investigation

329

287

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“…43 Substance P Substance P (neurokinin1) is a neuropeptide, released from sensory nerve fibers by PAR-2, and appears to potentiate itch by releasing histamine from dermal mast cells. 8,19 Topical capsaicin depletes substance P from cutaneous nerve terminals and destroys C-fibers to relieve itch.…”

Section: Nerve Growth Factormentioning

confidence: 99%

“…Naloxone and naltrexone, drugs that block opiate receptors, have been used to treat cholestatic pruritus. 8 …”

Section: Opioid and Cannabinoid Peptidesmentioning

confidence: 99%

Wound pruritus: pathophysiology and management

Paul

2015

CWCMR

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Purpose: The objective of this article is to review literature on wound pruritus, with a focus on summarizing pathophysiology and management. Method: Literature related to the physiology of itch was reviewed. PubMed, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Embase were searched for all research studies written in English which include "wound" (injury/burn) and "pruritus" (itch) in the title or abstract. Articles were accepted if they involved wounds or acute burns. Literature related to options for management of wound pruritus was reviewed. Results: While all types of wounds can be the source of associated pruritus, most studies have been done concerning pruritus associated with burns. There are treatment options for pruritus which can be considered for management of wound pruritus. Conclusion: Further research is indicated to gain insights into the problem of wound pruritus. As more is learned about the physiology of wound pruritus, more effective management strategies can be developed and employed.

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“…However, recently, despite these problems, some progress has been made in understanding the pathophysiology of itch, with exciting potential for the development of new anti-itch treatments. Most importantly, it is becoming generally recognized that the symptom of itch can be a result of intracutaneous ("pruritoceptive") or central (within the central nervous system) "neurogenic" pathomechanisms, or both [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis and Treatment of Pruritus

Greaves

2010

Curr Allergy Asthma Rep

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Classification of itch into four categories-pruritoceptive, neurogenic, neuropathic, and psychogenic-has proven to be of utility to clinicians and investigators. Itch is recognized to be transmitted by dedicated afferent neurons, and a matrix of cerebral cortical loci involved in perception and the desire to scratch has been recognized. This highlights the multidimensional nature of the itch sensation. Some of the many mediators of itch, especially relevant in pruritogenic itch, are the result of cross-talk between dermal mast cells and adjacent cutaneous afferents. Keratinocytes of the epidermis express many neuropeptides, and their receptors are far from passive bystanders in the neurophysiology of itch. Mediators can also act centrally (eg, opioid peptides that act on micro receptors in the central nervous system). The pathophysiology of pruritus in neurogenic itch caused by common systemic diseases is gradually being elucidated, especially in the itch of cholestasis, although the molecular basis of itching in chronic renal failure remains elusive. Better understanding of the mediators of itch and their receptors has led to the imminent development of novel anti-itch compounds, including interleukin-31 inhibitors, histamine H4-receptor antagonists, and neurokinin-1 receptor antagonists.

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Itch: More than Skin Deep

Cited by 59 publications

References 24 publications

Frontiers in pruritus research: scratching the brain for more effective itch therapy

Frontiers in pruritus research: scratching the brain for more effective itch therapy

Wound pruritus: pathophysiology and management

Pathogenesis and Treatment of Pruritus

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