The molecular and cellular mechanisms of itch and the involvement of TRP channels in the peripheral sensory nervous system and skin

Abstract

Itch is an unpleasant cutaneous sensation that can arise following insect bites, exposure to plant ingredients, and some diseases. Itch can also have idiopathic causes. Itch sensations are thought to protect against external insults and toxic substances. Although itch is not directly lethal, chronic and long lasting itch in certain diseases can worsen quality of life. Therefore, the mechanisms responsible for chronic itch require careful investigation. There is a significant amount of basic research concerning itch, and the effect of various itch mediators on primary sensory neurons have been studied. Interestingly, many mediators of itch involve signaling related to transient receptor potential (TRP) channels. TRP channels, especially thermosensitive TRP channels, are expressed by primary sensory neurons and skin keratinocytes, which receive multimodal stimuli, including those that cause itch sensations. Here we review the molecular and cellular mechanisms of itch and the involvement of TRP channels in mediating itch sensations.

Itchy channels and where to find them

“…In these experiments the absence of TRPA1 and/or TRPV1 channel activity in the fibre has been confirmed with allyl isothiocyanate (AITC) and capsaicin, respectively. Evidence presented herein argues strongly against the important role of TRP channels in the itch signal initiation at the level of free nerve endings of the cutaneous itch fibres, which is in stark contrast to the body of previous literature on the role of TRP channels in itch (see Kittaka & Tominaga, for review).…”

Itch: From mechanism to (novel) therapeutic approaches

“…GPCRs promote the opening of ion channels (eg, transient receptor potential cation channels, especially transient receptor potential vanilloid 1 [TRPV1] and transient receptor potential ankyrin 1 [TRPA1], and voltage-gated sodium channels [Na V s]) to generate action potentials (Fig 1). 4 In addition to GPCRs, various external stimuli can also activate TRPV1 and TRPA1 (eg, extracellular pH, ATP, prostaglandins, oxidants, capsaicin [for TRPV1], heat [>428C for TRPV1], allyl isothiocyanate [found in wasabi; for TRPA1], and cold [<178C for TPRA1]). 5,6 There are 2 subtypes of itch-sensitive neurons that are entirely separate and independent: histaminergic neurons and nonhistaminergic neurons.…”

Antipruritic Effect of Natural Coumarin Osthole through Selective Inhibition of Thermosensitive TRPV3 Channel in the Skin

“…Many studies on C. monnieri have focused on antipruritic action of the extracts as well as the ingredients purified from the plant extracts in rodent animal models. Yet, the critical ingredients from the C. monnieri plant used for antipruritus and their mechanisms of action still remain elusive, although Yang et al (2016) recently reported that osthole inhibits capsaicin-induced calcium influx and inward TRPV1 current in cultured small dorsal root ganglion neurons in which other TRPs channels are also expressed (Kittaka and Tominaga, 2017).…”

“…Although acute itch is considered to be a defense mechanism that alerts the body to remove irritants, transient itching can progress to become persistent and chronic (Zhang, 2015). Chronic itch can be a widespread symptom of systemic diseases, including atopic dermatitis, liver disease, kidney failure, cholestasis, diabetes, and cancers (Mollanazar et al, 2016;Kittaka and Tominaga, 2017). Due to its complex underlying mechanism, chronic itch as an unmet medical need presents a serious health issue which affects upward of 20% of people worldwide (Meng and Steinhoff, 2016).…”