Itch, Tickle, and Tingle

Itch

Itch is defined as an unpleasant sensation associated with the desire to scratch. Itch is commonly evoked by insect bites, allergic reactions, or contact with certain plants such as poison ivy or cowhage, a bean plant with seedpods that are covered with spicules that cause itch when they contact skin. Allergic reactions such as hives are caused by the release of histamine in the skin, which elicits a nearly pure sensation of itch and associated reddening of the skin (flare). Histamine excites a particular class of thin (unmyelinated), touch-insensitive nerve endings that transmit impulses to the spinal cord and, from there, to higher centers in the brain to result in itch sensation. Itch caused by histamine release is usually relieved by antihistamines. Interestingly, itch from cowhage does not involve histamine but, rather, a different chemical called mucunain. Mucunain is contained within the cowhage spicules that cause itch without a flare reaction [Page 510]when they contact the skin. Mucunain is a protease that interacts with protease-activated receptors (PARs) that reside on sensory nerve endings in the skin. It is currently under investigation if mucunain activates a separate class of touch-sensitive nerve endings in the skin that transmit itch independently of histamine. The existence of a histamine-indepen-dent itch pathway has great significance for patients who suffer from chronic itch caused by liver and kidney disease, AIDS, and many other diseases and skin conditions in which the itch is not relieved by antihistamines. A better understanding of this type of itch will hopefully lead to new and improved treatments for chronic itching.

Itch is often considered to be a low level of pain sensation. However, several observations suggest that itch is distinct from the sensation of pain. Itch warns the organism of insects or plants contacting the skin surface, which can then be protectively removed by scratching or rubbing. In contrast, a painful stimulus usually evokes protective withdrawal of the stimulated skin area away from the stimulus, rather than scratching, which would worsen the pain. Scratching is itself a mild form of pain that relieves itch. Morphine, which reduces pain, frequently causes itching. Experimental studies have shown that electrical stimulation at certain discrete sites on the skin can evoke a sensation of itch; increasing the frequency of stimulation evokes a stronger itch sensation that never becomes painful. Despite these distinctions between itch and pain, it is still not certain if they are conveyed by their own separate pathways. Both painful and itchy sensations activate largely overlapping brain regions including the somatosensory and supplementary motor cortex, insula, and anterior cingulate gyrus. Furthermore, although pain, itch, and temperature are all conveyed primarily by the spinothalamic tract, current evidence suggests that itchy and painful stimuli excite a common set of neurons rather than distinct subpopulations of itch- and pain-specific neurons. Increased research interest in this question could answer whether itch and pain are conveyed by separate or shared pathways.

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