![]() ![]() ![]() Pruritogens either directly or indirectly cause activation of either TRPA1 or TRPV1 ion channels in most cases, or less reported via TRPV4, to lower the activation threshold of itch fibers to generate an action potential ( 8). The transient receptor potential (TRP) channels comprise 28 members in mammals and 27 in humans that are categorized based on amino acid sequence homology, including TRPA, TRPM, and TRPV ( 7). Referred itch occurs when overlapping sensory distribution of nerves or the pathways of nerve activation is coupled with depolarization of the nerve ( 5, 6). The site of itch stimulates local neuropeptide release and can activate neurosensory signals that communicate with the somatosensory and motor cortex, leading to itch localization and cognitive awareness of the itch stimuli ( 1, 3). Neurosensory signals may involve the well-known axon reflex arc, including signaling via the dorsal root ganglion, in addition to local activation and local release of neuropeptides, which is known as the antidromic reflex. Ongoing research suggests co-signaling of pain and itch sharing the same sensory fibers as well as specific itch-signaling sensory fibers, and it is plausible that both mechanisms exist ( 1). Of the C-fibers there are histamine-dependent and histamine-independent pruritogenic fibers ( 4). Itch is detected by nociceptors and free nerve endings, which in turn excite unmyelinated C-fibers and thinly myelinated Aδ nerve fibers ( 3). Most of the literature on the mechanisms and mediators involved in itch is based on our understanding of itch in the skin, also known as pruritoceptive itch, which is generated in the skin by pruritogens either through inflammation via various chemical mediators or skin damage ( 1, 2). This review invites readers to appreciate itch beyond the skin by highlighting several specific itch patterns-nasal, oral, auricular, vulvovaginal, anal, and perineal itch-the pathophysiological mechanisms that underlie them, the clinical patterns these may cause, and some unique treatments. Despite itch being an ancient reflex and evolutionarily conserved phenomenon, better clinical understanding of the nuances between sites of itch sensation may lead to improved clinical outcomes. Less understood and considered are the physiological processes involved in the itching sensation that occurs at mucosal and junctional dermal sites, which is extraordinary as from an evolutionary point of view these sites serve important guardian roles, rich in sensory nerves and inflammatory cells. We traditionally think of itch as a sensation of the skin related to allergy, an insect sting or interestingly, anxiety and frustration. Itch is a nociceptive sensation linked with reflexes and cognitive motor actions. 3Clinical Medicine, Griffith University, Southport, QLD, Australia. ![]() 2Cingulum Health, Sydney, NSW, Australia.1LifeSpan Medicine, Los Angeles, CA, United States.Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Common colds: protect yourself and others.įood and Drug Administration. Predictors of biphasic reactions in the emergency department for patients with anaphylaxis. Candida infections of the mouth, throat, and esophagus. doi:10.1007/s4025-3Ĭenters for Disease Control and Prevention. Toxic side effects of targeted therapies and immunotherapies affecting the skin, oral mucosa, hair, and nails. Pollen food allergy syndrome.Īmerican Academy of Allergy Asthma and Immunology. American College of Allergy, Asthma, and Immunology. ![]()
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