Modulation of Itch by Localized Skin Warming and Cooling.
Sanders Kristen M,Hashimoto Takashi,Sakai Kent,Akiyama Tasuku
Skin thermal changes modulate itch sensitivity. However, the mechanisms of this modulation are still unclear. Using mouse models of acute and chronic itch, we investigated whether local innocuous thermal stimulation of the skin alters itch sensitivity and if blockade of thermosensitive transient receptor potential (TRP) channels can reduce these changes. Localized thermal changes were achieved by placing a thermal probe in contact with the back skin for 30 s. Warming the skin significantly increased serotonin-evoked scratching and spontaneous scratching in the ovalbumin model of atopic dermatitis but decreased histamine-evoked scratching. These changes were blocked by a TRPV4 antagonist. Cooling the skin significantly increased serotonin-evoked scratching but reduced histamine-evoked scratching. The increase in serotonin-evoked scratching, but not the reduction of histamine-evoked scratching, was blocked by TRPM8 antagonism. Chloroquine-evoked scratching was unaffected by either warming or cooling. Our data indicate that different itch signaling pathways are differentially modulated by skin thermal changes.
Effects of Short-term Temperature Change in the Innocuous Range on Histaminergic and Non-histaminergic Acute Itch.
Lewis Zoe,George David N,Cowdell Fiona,Holle Henning
While temperatures in the noxious range are well-known to inhibit acute itch, the impact of temperature in the innocuous temperature range is less well understood. We investigated the effect of alternating short-term temperature changes in the innocuous range on histamine and cowhage-induced acute itch, taking into account individual differences in baseline skin temperature and sensory thresholds. Results indicate that cooling the skin to the cold threshold causes a temporary increase in the intensity of histamine-induced itch, in line with previous findings. Skin warming increased cowhage-induced itch intensity. Potential mecha-nisms of this interaction between thermosensation and pruritoception could involve cold-sensitive channels such as TRPM8, TREK-1 or TRPC5 in the case of histamine. The rapid modulation of cowhage induced itch - but not histamine-induced itch - by transient skin warming could be related to the lower temperature threshold of pruriceptive polymodal C-fibres (cowhage) as compared to the higher temperature threshold of the mechanoinsensitive C-fibres conveying histaminergic itch.
Why we scratch an itch: the molecules, cells and circuits of itch.
Bautista Diana M,Wilson Sarah R,Hoon Mark A
Itch is described as an irritating sensation that triggers a desire to scratch. However, this definition hardly seems fitting for the millions of people who suffer from intractable itch. Indeed, the Buddhist philosopher Nāgārjuna more aptly stated, "There is pleasure when an itch is scratched. But to be without an itch is more pleasurable still." Chronic itch is widespread and very difficult to treat. In this review we focus on the molecules, cells and circuits in the peripheral and central nervous systems that drive acute and chronic itch transmission. Understanding the itch circuitry is critical to developing new therapies for this intractable disease.
Peripheral and Central Mechanisms of Itch.
Dong Xintong,Dong Xinzhong
Itch is a unique sensory experience that is encoded by genetically distinguishable neurons both in the peripheral nervous system (PNS) and central nervous system (CNS) to elicit a characteristic behavioral response (scratching). Itch interacts with the other sensory modalities at multiple locations, from its initiation in a particular dermatome to its transmission to the brain where it is finally perceived. In this review, we summarize the current understanding of the molecular and neural mechanisms of itch by starting in the periphery, where itch is initiated, and discussing the circuits involved in itch processing in the CNS.
Clinical presentation, management, and pathophysiology of neuropathic itch.
Steinhoff Martin,Schmelz Martin,Szabó Imre Lőrinc,Oaklander Anne Louise
The Lancet. Neurology
Unlike conventional itch, neuropathic itch develops in normal skin from excess peripheral firing or dampened central inhibition of itch pathway neurons. Neuropathic itch is a symptom of the same central and peripheral nervous system disorders that cause neuropathic pain, such as sensory polyneuropathy, radiculopathy, herpes zoster, stroke, or multiple sclerosis, and lesion location affects symptoms more than aetiology. The causes of neuropathic itch are heterogeneous, and thus diagnosis is based primarily on recognising characteristic, disease-specific clinical presentations. However, the diagnosis of neuropathic itch is challenging, different subforms exist (eg, focal vs widespread, peripheral vs central), and the mechanisms of neuropathic itch are poorly understood, resulting in reduced treatment availability. Currently available strategies include treating or preventing causal diseases, such as diabetes or herpes zoster, and topical or systemic medications that calm excess neuronal firing. Discovery of itch mediators such as gastrin releasing peptide, receptors (eg, neurokinin-1), and pathways (eg, Janus kinases) might encourage much needed new research into targeted treatments of neuropathic itch.
Itch: A Paradigm of Neuroimmune Crosstalk.
Wang Fang,Kim Brian S
Although the medical definition of itch has been in existence for 360 years, only in the last 20 years have we begun to understand the basic mechanisms that underlie this unique sensation. Therapeutics that specifically target chronic itch as a pathologic entity are currently still not available. Recent seminal advances in itch circuitry within the nervous system have intersected with discoveries in immunology in unexpected ways to rapidly inform emerging treatment strategies. The current review aims to introduce these basic concepts in itch biology and highlight how distinct immunologic pathways integrate with recently identified itch-sensory circuits in the nervous system to inform a major new paradigm of neuroimmunology and therapeutic development for chronic itch.
The vicious cycle of itch and anxiety.
Sanders Kristen M,Akiyama Tasuku
Neuroscience and biobehavioral reviews
Chronic itch is associated with increased stress, anxiety, and other mood disorders. In turn, stress and anxiety exacerbate itch, leading to a vicious cycle that affects patient behavior (scratching) and worsens disease prognosis and quality of life. This cycle persists across chronic itch conditions of different etiologies and even to some extent in healthy individuals, suggesting that the final common pathway for itch processing (the central nervous system) plays a major role in the relationship between itch and anxiety. Pharmacological and nonpharmacological treatments that reduce anxiety have shown promising anti-itch effects. Further research is needed to establish specific central mechanisms of the itch-anxiety cycle and provide new targets for treatment.
Physiology and Pathophysiology of Itch.
Cevikbas Ferda,Lerner Ethan A
Itch is a topic to which everyone can relate. The physiological roles of itch are increasingly understood and appreciated. The pathophysiological consequences of itch impact quality of life as much as pain. These dynamics have led to increasingly deep dives into the mechanisms that underlie and contribute to the sensation of itch. When the prior review on the physiology of itching was published in this journal in 1941, itch was a black box of interest to a small number of neuroscientists and dermatologists. Itch is now appreciated as a complex and colorful Rubik's cube. Acute and chronic itch are being carefully scratched apart and reassembled by puzzle solvers across the biomedical spectrum. New mediators are being identified. Mechanisms blur boundaries of the circuitry that blend neuroscience and immunology. Measures involve psychophysics and behavioral psychology. The efforts associated with these approaches are positively impacting the care of itchy patients. There is now the potential to markedly alleviate chronic itch, a condition that does not end life, but often ruins it. We review the itch field and provide a current understanding of the pathophysiology of itch. Itch is a disease, not only a symptom of disease.