Recent studies show that a new class of C fibers with an exceptionally lower conduction velocity and insensitivity to mechanical stimuli can likely be considered as afferent units that mediate the itchy sensation . Indeed, this subjective feeling has been extensively investigated but no explanation of the individual susceptibility to the itching sensation, without any sign of coexisting dermatitis, has been found. Laboratory investigation of the itch response has also been limited.
An itch response can be experimentally induced by topical or intradermal injections of various substances such as proteolytic enzymes, mast cell degranulators, and vasoactive agents. Histamine injection is one of the more common procedures: histamine dihydroclo-ride (100 |g in 1 mL of normal saline) is injected intradermally in one forearm. Then, after different time intervals, the subject is asked to indicate the intensity of the sensation using a predetermined scale and the duration of itch is recorded. Information is always gained by the subject's self-assessment.
A correlation between whealing and itching response, produced by applying a topical 4% histamine base in a group of healthy young females, has been investigated by Grove. The itching response was graded by the subjects using the following scale: none, slight, moderate, and intense. The data showed that, despite the fact that 90% of the wheals were greater than 8 mm in diameter, only 50% of the subjects experienced pruritus; patients with large wheals often had no complaints of itching, suggesting that the dimensions of the wheals do not correlate well with pruritus. In addition, itch and sting perception seem to be poorly correlated. Grove  compared the cumulative lactic acid sting scores with the histamine itch scores in 32 young subjects; all the subjects who were stingers were also moderate to intense itchers, while 50% of the moderate itchers showed little or no stinging response.
Yosipovitch , studying the effects of drugs on C fibers during experimentally induced itch, showed that topically applied aspirin rapidly decreases histamine-induced itch. This result can be attributed to the role that prostaglandines play in pain and itch sensation . Localized itching, burning, and stinging can also be a feature of nonimmu-nological contact urticaria. This condition, still not completely defined, is characterized by a local wheal and flare after exposure of the skin to certain agents. Different combinations of mediators such as non-antibody-mediated release of histamine, prostaglandins, leukotriens, substance P, and other inflammatory mediators may likely be involved in the pathogenesis of this disorder . The fact that prostaglandins and leukotriens may play a role in the inflammatory response is supported by the inhibition of the common urticants by both oral acetylsalicylic acid and indomethacin and by topical diclofenac and naproxen gel . Several substances, such as benzoic acid, cinnamic acid, cinnamic aldehyde, and nicotinic acid esters, are capable of producing contact nonimmunological urticaria, eliciting local edema and erythematous reactions in half of the individuals. Provocative tests
are usually used to identify subjects experiencing this condition: benzoic acid, sorbic acid, or sodium benzoate in open application well reproduce the typical symptoms in subjects suspected of contact nonimmunological urticaria.
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